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For Decision Makers in Managed Care Quarter 1 2010 Enjoy a cup of coffee on us! Complete our reader survey inside, and we’ll send you a Starbucks gift card. Diagnosis, Prognostic Factors, and Treatment Considerations for Prostate Cancer Prostate Cancer in 2010 Consultations: Where Do You Want to Go Next? Adapting to Economic Uncertainty PRSRT STD US Postage PAID Long Prairie MN Permit # 871 mco contents departments 3 Calendar of Events Quarter 1 | 2010 | Issue 1 features 13 Industry Thought Leaders A Discussion with Gary J. Tereso, PharmD, Manager of Pharmacy Services, Health New England, Inc. Managed Care Oncology recently sat down with Gary J. Tereso, Manager of Pharmacy Services for Health New England, Inc., to gain his insights on high-quality, cost-effective care in the oncology speciality. 21 Practical Perspective Adapting to Economic Uncertainty: The Transition from a Traditional Physician Practice Model to a True Business Model in Oncology by Beau Donegan, MBA, CEO, Newport Pacific Medical Associates Although oncology practices have been able to operate outside of the standard business model since their inception, the recent financial crunch necessitates a new way of looking at things. 24 Drug Therapy Reviews Prostate Cancer in 2010 by Charles J. Ryan, MD, Assistant Clinical Professor, University of California, San Francisco School of Medicine Prostate cancer is the most common noncutaneous cancer in men in the U.S., and it is the sixth most common cancer in the world. The current lifetime risk for prostate cancer in U.S. men is estimated at one in six. 32 Drug & Administration Compendia Coding, reimbursement, and available therapies in the treatment of prostate cancer. 48 Regulatory & Reimbursement Dates and locations of upcoming meetings, workshops, and conferences of interest to managed care oncology professionals. 5 Correspondence by Kjel A. Johnson, PharmD, Publisher, Managed Care Oncology We need to set reasonable expectations of when to say when. The combination of not behaving well and then expecting every possible type of treatment, regardless of the cost and likelihood of results, is not a sustainable care model. 6 Facts & Figures Data and accompanying graphics regarding the five-year survival rate for prostate cancer overall, by staging at diagnosis, and more. 16 Pipeline Report Investigational Agents for the Treatment of Prostate Cancer by Howard “Skip” Burris, MD, Director of Drug Development, The Sarah Cannon Research Institute 40 Clinical Trial Update by John W. Mucenski, BS, PharmD, Director of Pharmacy Operations, UPMC Cancer Centers A review of recent clinical trials in the treatment of prostate cancer. Included are the methods, results, conclusions, and managed care implications of each trial reviewed. 54 Resources & References A comprehensive list of prostate cancer sources relevant to managed care oncology professionals. advertising index Consultations: Where Do You Want to Go Next? by Roberta L. Buell, Managing Partner, Sausalito Healthcare Partners, and Principal Content Development, E-Expert Reimbursement Partners As of January 1, 2010, Medicare no longer pays Medicare Part B consultation codes. Why did Medicare eliminate these consults? What is it doing in terms of coding and payment, and how does this fit or not fit with nongovernment payors? 2 managedcareoncology Quarter 1 2010 IFC, 1..................................................................... Millennium Page 4 ................................................................................. Lilly Pages 11-12 ........................................................................Eisai Pages 19-20 ..............................................................Genentech BC...................................................................................Amgen Your opinion matters to us. We want to ely Valu able ry V alua ble | Sli ght ly V alua | No ble t Va luab le | Di d No t Re ad | Ve trem 3. How valuable did you find the information in each of the 2009 Managed Care Oncology journals? No Opinion | Ex Somewhat Useful Not Useful at All [a] Advertisements [b] Calendar of Events [c] Clinical Trial Update [d] Drug & Administration Compendia [e] Drug Therapy Reviews [f] Facts & Figures [g] Improving Value [h] Industry Thought Leaders [i] Pipeline Report [j] Regulatory & Reimbursement [k] Resources & References | Ve trem ely Valu a ble ry V alua ble | Sli ght ly V alua | No ble t Va luab le | Di d No t Re ad [a] Leukemia (Q1 2009) [b] Cervical Cancer (Q2 2009) [c] Pancreatic Cancer (Q3 2009) [d] Melanoma (Q4 2009) 4. How valuable do you find each of the following features? (These features are included in every issue of the Managed Care Oncology journal.) Managed Care Oncology? __________________________________ 2. Overall, do you find the information in Managed Care Oncology to be: Very Useful Not too Useful 5. What topics would you like to see addressed more, or added to, 6. How important will each of the following be to you as a source of information on chemotherapy trends in 2010? ely Valu able ry V alua ble | Sli ght ly V alua | No ble t Va luab le No Opinion | Ve Positive Very Negative trem Very Positive Negative know what you think about Managed Care Oncology. Fill out and return the survey below for a $5 Starbucks gift card. We’ll use your responses to plan future issues of the journal. | Ex 1. What is your overall opinion of Managed Care Oncology? | Ex ▼ detach here and mail today ▼ reader survey [a] Printed journals Which is the most important one? ________________________________ [b] Electronic journals or e-newsletters Which is the most important one? ________________________________ [c] Web sites Which is the most important one? ________________________________ [d] Mailings from professional associations Which is the most important one? ________________________________ [e] Pharmaceutical company representatives [f] Other (please describe)____________________________________ 7. What do you do with this publication after reading it? Keep it for reference Pass it along to another person Discard or recycle it 8. Which position or type of organization most closely matches your role? Consultant Health plan management or medical director (pharmacy or medical) Oncologist Pharmaceutical company Practice or office manager Other (please describe)____________________________________ second, fold this panel down and tape shut. make sure the mail panel is visible. FOR ADDITIONAL INFORMATION PLEASE CONTACT THE US POSTAL SERVICE REPRESENTATIVE BELOW: BUSINESS REPLY MAIL FIRST-CLASS MAIL PERMIT NO 967 EvANSTON IL 60201-9938 CK=2 TO BE USED ONLY WITH FIM - C (Business Reply Mail) AND ZIP CODE: 60201-9938 CK=2 CAUTION: POSTAGE WILL BE PAID BY ADDRESSEE USE ONLY FOR ADDRESS BEARING THE ZIP+4 CODE ABOVE. SEE PUBLICATION 353 FOR PRINTING REQUIREMENTS. CAUTION: RESEARCH ASSOCIATES USE ONLY FOR ADDRESS BEARING THE ZIP+4 CODE ABOVE. SEE PUBLICATION 353 FOR PRINTING REQUIREMENTS. 909 DAvIS ST STE 600 EvANSTON IL 60201-9938 ALIGN WITH LOWER ALIGN RIGHT WITH CORNER LOWER RIGHT CORNER first, fold this panel up along line. BUSINESS REPLY MAIL 1 OZ. ONLY PERMIT NO. 967 EVANSTON IL THIS POSITIVE PREPARED FOR: Your opinionTHISmatters to us. POSITIVE PREPARED FOR: BUSINESS REPLY MAIL 1 OZ. ONLY RESEARCH ASSOCIATES PERMIT NO. 967 EVANSTON IL 909 DAVIS ST STE 600 Your opinions about Managed Care Oncology are essential to our planning. Return this EVANSTON survey, and you IL will60201-9938 RESEARCH receive a $5 Starbucks gift card. Simply complete the survey, detach, fold, seal, and mail. No poStage iSASSOCIATES 909 DAVIS STE 600 (c) 1989-2009 Envelope Manager version 3.011.006. Created January ST 23, 2009 6:30 PM RequiRed. We’ll use your responses to plan future issues of the journal. EVANSTON IL 60201-9938 Use Envelope Manager's DAZzle Designer to create a complete courtesy or business reply mail artwork in minutes! Name (c) 1989-2009 Envelope Manager version 3.011.006. Created January 23, 2009 www.EnvelopeManager.com (800) 576-3279 6:30 PM Use Envelope Manager's DAZzle Designer to create a complete courtesy or business reply mail artwork in minutes! Address City www.EnvelopeManager.com State (800) 576-3279 ZIP Telephone E-mail ********************************************************************************** ▼ detach here and mail today ▼ ALIGN WITH UPPER NO POSTAGE FOR ADDITIONAL INFORMATION ALIGN RIGHT PLEASE CONTACT THE US POSTAL SERVICE NECESSARY WITH REPRESENTATIVE BELOW: CORNER IF MAILED UPPER IN THE RIGHT UNITED STATES TO BE USED ONLY WITH FIM - C (Business Reply Mail) CORNER AND ZIP CODE: For Decision Makers in Managed Care calendar of events The list of events that follows provides the dates and loca tions of upcoming meetings, workshops, and conferences of interest to managed care oncology professionals. May 4-7 13-16 Armada Health Care Sixth Annual Specialty Pharmacy Summit Las Vegas, Nevada California Association of Physician Groups Healthcare Conference Palm Desert, California June 4-8 Annual Meeting for the American Society of Clinical Oncology Chicago, Illinois 9-11 Institute 2010 for America’s Health Insurance Plans Las Vegas, Nevada Publishing Office StayWell Custom Communications 909 Davis St., 6th Floor Evanston, IL 60201 800-543-3854 www.staywellcustom.com Published by: Magellan/ICORE Healthcare 5850 T.G. Lee Blvd., Suite 510 Orlando, FL 32822 Tel: 866-66i-core Fax: 866-99i-core [email protected] www.icorehealthcare.com Senior Account Manager Judith Kass [email protected] Publishing Staff Publisher Kjel A. Johnson, PharmD Manufacturing Manager Linda Kastler [email protected] Media Manager Erika Ruiz-Colon Advertising and Sales For information on advertising in Managed Care Oncology, contact: Tom Corcoran 440-543-1548 [email protected] Senior Editor Laura Semko [email protected] © 2010 Magellan/ICORE Healthcare. Managed Care Oncology is published in conjunction with StayWell Custom Communications. All rights reserved. All trademarks are the property of their respective owners. Printed in the U.S.A. The content of Managed Care Oncology – including text, graphics, images, and information obtained from third parties, licensors, and other material (“Content”) – is for informational purposes only. The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Managed Care Oncology does not verify any claims or other information appearing in any of the advertisements contained in the publication and cannot take responsibility for any losses or other damages incurred by readers in reliance on such content. Managed Care Oncology Editorial Advisory Board Chandra P. Belani, MD Miriam Beckner Professor of Medicine, Penn State College of Medicine; Deputy Director, Penn State Cancer Institute at Penn State Milton S. Hershey Medical Center Howard A. “Skip” Burris III, MD Director of Drug Development, The Sarah Cannon Research Institute Richard Cook, PharmD Pharmacy Manager, Clinical and Quality Programs, Blue Care Network of Michigan Jeffrey Crawford, MD Chief of Medical Oncology, Duke University Medical Center William J. Gradishar, MD Professor of Medicine, Director of Breast Medical Oncology, Northwestern University, Feinberg School of Medicine Cliff Hudis, MD Chief, Breast Cancer Medicine Service, Memorial Sloan Kettering Cancer Center Deborah Partsch, PharmD Director, Pharmacy Operations, Highmark Blue Cross Blue Shield Jeffrey Patton, MD Medical Director, Tennessee Oncology Dan Petrylak, MD Associate Professor of Medicine, Columbia University Medical Center Don’t Miss an Issue! New online link makes it easy to manage your subscription. We have a new way to subscribe, unsubscribe, and edit your subscription information for Managed Care Oncology. If you would like to subscribe to this publication, please use the link below. If you already receive this magazine regularly, we’d like you to confirm your subscription information so you don’t miss an issue. Visit www.ManagedCareOncology.com/subscribe and complete the brief form. Then, if anything changes, it will be easy to update your information. Thanks, and we hope you find the magazine useful. managedcareoncology.com 3 1-866-4PatOne Today, he got the cancer treatment he needed. Along with a healthy dose of peace of mind. Lilly Oncology A cancer diagnosis gives a patient a lot to worry about. The truth is, it can also cause treatment concerns for physicians as well as reimbursement and coverage issues for practice administrators and insurers. Call us or visit our Web site to learn how we can partner with you to simplify it all. It’s the kind of support you need, while patients receive the treatment they need. For more information, visit www.LillyPatientOne.com or call 1-866-4PatOne (1-866-472-8663). Patient Assistance MQ43286 0907 PRINTED IN USA © 2007, ELI LILLY AND COMPANY. ALL RIGHTS RESERVED. Insurance Expertise Claim Appeals correspondence “No Thanks” Last year, I outlined a pretty shocking fact: Upward of half of all cancer deaths are preventable. I contemplated what was easier – preventing cancer or treating it? When you stop to look at the cure rates for some of our most prevalent cancers at the stages they often present themselves at diagnosis – lung, colorectal, and breast – prevention is the way to go. But getting people to behave isn’t easy. A few years ago, I was at a conference with an oncologist who had grown up in, shall we say, a war-torn area of the world. He had a great line: “You know what is wrong with cancer care in the U.S.? I will tell you. In my country, we expect to die; in Europe, they say, ‘Hey, guess what? I am gonna die.’ But in the U.S., there is an expectation that immortality is an option.” Maybe he is on to something. I can tell you this: The combination of not behaving well and then expecting every possible type of treatment, regardless of the cost and likelihood of results, especially late in life, is not a sustainable care model. In January of this year, the Journal of Oncology Practice published a pathway study.1 In this retrospective study of non-small-cell lung cancer (90% preventable, by the way), the authors found that patients whose physician historically followed a pathway by chance (the pathway was not implemented but rather appeared to be followed) experienced lower costs than the patients who had a physician who did not appear to follow clinical evidence. Most interesting to me was this: The general hypothesis has always been that if you follow a treatment guideline, hospital costs will be reduced. This was not found; in fact, there was no difference in outpatient or acute care visits. Rather, the cost difference was associated with a reduction in drug costs. After a detailed review of the study, 1% of the “pathway” group received third- to sixth-line therapy while the “offpathway” group had 32% receiving third- to sixth-line therapy. I think I found why drug costs were reduced – we need to set reasonable expectations of when to say when. Frankly, we have been helping payors do this for years. It’s comforting to know that when we counsel oncologists that these lines of therapy are experimental (at best) and not covered under the payor’s certificate of coverage, oncologists Reference agree with us and don’t appeal the recommendation. In fact, they are commonly relieved to have an answer for the patient who wants “no holds barred.” On the morning that I was authoring this correspondence (literally), I received a call that my grandfather had died of acute myelogenous leukemia (AML). He had a great life – he loved to smoke a cigar once in a while but never more than a few in a month. He enjoyed an occasional glass of wine with dinner or a beer at a ball game. Red meat portions were small; physician appointments and tests were always on schedule. He was a pastor and told me that it was stressful, but there must be some peace-of-mind employment benefits with that job! I guess they call such a lifestyle “moderate.” He was diagnosed with AML 18 months ago and was told that he had three to six months to live if he did not receive one of several chemotherapy treatments. When his oncologist told him what the treatments would do for survival and quality of life, he said, “No thanks.” Instead, he just went in for a transfusion once a month at a few hundred dollars a clip. He then went on to enjoy life for another year and a half. No heroics, no fifth-line chemotherapy, and although he tried both a colony-stimulating factor and an erythropoietin-stimulating agent, when they didn’t make him feel any better, he stopped them. So … why do I think about his care in a journal committed to delivering highquality, cost-effective care? His moderate lifestyle and comfort in dying gave him a very long and high-quality life. For 98 years. Here’s to you, Grandpa. And please don’t forget to let me know if they serve occasional beers in moderation at the games up there. Kjel A. Johnson, PharmD, Publisher Managed Care Oncology 1. Neubauer MA, Hoverman JR, Kolodziej M, et al. Cost-effectiveness of evidence-based treatment guidelines for the treatment of non-small-cell lung cancer in the community setting. J Oncol Pract. 2010;6(1):12-18. managedcareoncology.com 5 facts & figures In every issue, Facts & Figures provides snapshots of information key to managed care oncology professionals. This installment features data and accompanying graphics regarding the fiveyear survival rate for prostate cancer overall and by stage at diagnosis, the probability of developing prostate cancer, and more. In addition, we have expanded this feature to include “Stakeholder Insights” and “Claims Benchmarks.” We hope you find these new elements of value as you review your internal plan data. This issue of Managed Care Oncology discusses one of the most treatable cancers – prostate cancer. According to the American Cancer Society, the latest 2009 estimates for prostate cancer in the U.S. are that: ■ About 192,280 new cases of prostate cancer will be diagnosed. ■ 27,360 men will die of prostate cancer. Of patients diagnosed with localized or regional prostate cancer, 100% survive at least five years from diagnosis, and 31% of those with distant prostate cancer survive five years after diagnosis. Cancer of the Prostate (Invasive), Five-Year Relative Survival Rate by Stage at Diagnosis, Percent 1999 to 2005 100% 99.7% 100% 100% 90% Percent Survival 80% 75.5% 70% 60% 50% 40% 30% 30.6% 20% 10% 0% All Stages Localized Regional Distant Unstaged Stage at Diagnosis Source: American Cancer Society, 2009; National Cancer Institute Rates are from the SEER 17 areas (San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, Atlanta, San JoseMonterey, Los Angeles, Alaska Native Registry, Rural Georgia, California excluding SF/SJM/LA, Kentucky, Louisiana, and New Jersey). California excluding SF/SJM/LA, Kentucky, Louisiana, and New Jersey contribute cases for diagnosis years 2000 to 2005. The remaining 13 SEER areas contribute cases for the entire period 1999 to 2005. Rates are based on followup of patients into 2006. 6 managedcareoncology Quarter 1 2010 While there are highly effective treatments available, these high relative survival rates reflect the emphasis on early diagnosis, as the data below show that 81% of invasive prostate cancer was localized on diagnosis. Cancer of the Prostate (Invasive), Stage at Diagnosis, Percent 1999 to 2005 4% 3% 12% Localized Regional Distant Unstaged 81% Source: American Cancer Society, 2009; National Cancer Institute Rates are from the SEER 17 areas (San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, Atlanta, San JoseMonterey, Los Angeles, Alaska Native Registry, Rural Georgia, California excluding SF/SJM/LA, Kentucky, Louisiana, and New Jersey). California excluding SF/SJM/LA, Kentucky, Louisiana, and New Jersey contribute cases for diagnosis years 2000 to 2005. The remaining 13 SEER areas contribute cases for the entire period 1999 to 2005. Rates are based on followup of patients into 2006. The SEER incidence and U.S. death rates for prostate cancer illustrate that this disease is primarily one of older males (at least 65 and older), with African-American males having the highest death rate. SEER Incidence and U.S. Death Rates, Age-Adjusted and Age-Specific Rates, by Race Incidencea At Diagnosis/Death All ages Younger than 65 65 and older All ages (IARC world std)c All Races, Males White Males U.S. Deathsb Black Males All Races, Males White Males Black Males 159.3 153 239.8 25.6 23.6 56.3 57.2 54.7 101.2 1.9 1.6 5.1 864.9 832.8 1,198.0 190 176 410.4 107 103 167 11.1 10.1 25.7 Source: American Cancer Society, 2009; National Cancer Institute a. SEER 17 areas. Rates are per 100,000 and are ageadjusted to the 2000 U.S. standard population (19 age groups – Census P251130), unless noted. b. U.S. Mortality Files, National Center for Health Statistics, Centers for Disease Control and Prevention. Rates are per 100,000 and are ageadjusted to the 2000 U.S. standard population (19 age groups – Census P251130), unless noted. c. Rates are per 100,000 and are ageadjusted to the International Agency for Research on Cancer (IARC) world standard population. managedcareoncology.com 7 Stakeholder Insights Consistent with the SEER incidence data, a recent survey of urology practices conducted by ICORE Healthcare found that 69% of male patients undergoing LHRHa treatment for prostate cancer received coverage under Medicare, which is a slight increase from an ICORE Healthcare survey conducted in 2006. Percent of Prostate Cancer Patients Receiving LHRHa Who Are Covered by Medicare Percent of LHRHa Patients in Practice 100% 90% 80% 70% 60% 65% 69% 50% 40% 30% 20% 10% 0% 2006 2009 Source: ICORE Healthcare Survey of Physician Practices, 2006, 2009 Most of the LHRHa product was distributed to physicians directly through the manufacturer or a distributor. The percentage of LHRHa product obtained through specialty pharmacies has been increasing over the last few years. LHRHa Product Distribution to Physician Office 15% 19% 85% 81% 2006 2009 Manufacturer/Distributor Specialty Pharmacy to Office/Patient Source: ICORE Healthcare Survey of Physician Practices, 2006, 2009 8 managedcareoncology Quarter 1 2010 In the most recent survey, urologists reported that 67% of the LHRHa product volume used in their practice was Lupron. The next most utilized LHRHa reported was Eligard, with a 25% share of volume. Share of LHRHa Market Volume Reported by Urologists, 2009 4% 2% 2% 25% Eligard 1/3/4/6 month Lupron 1/3/4 month Trelstar 1/3 month Zoladex 1/3 month Vantas 12-month implantable 67% Source: ICORE Healthcare Survey of Physician Practices, 2009 Physician practices reported that, on average, five weeks elapse from billing for an LHRHa to reimbursement by private payors, whereas Medicare reimbursed slightly faster at 4.6 weeks. Average Time Between Billing and Physician Reimbursement for LHRHa Products, 2009 5 Private Payors 4.6 Medicare 0 1 2 3 4 5 6 Average Number of Weeks Source: ICORE Healthcare Survey of Physician Practices, 2009 The policy of the Centers for Medicare & Medicaid Services is a significant factor in LHRHa reimbursement to physicians. Quarterly average selling price (ASP) adjustments and least costly alternative (LCA) reimbursements can make purchasing and reimbursements challenging for physician practices. Healthcare reform may ultimately affect Medicare and reimbursements. What do you think? Whatever shape reform ultimately takes in relation to Medicare, all stakeholders – payors, providers, and patients – are in it together, so we all will have to wait and see. managedcareoncology.com 9 Claims Benchmarks For now, we took a look at the reality of paid prostate cancer-related claims from two large regional commercial payors. We analyzed 12 months of paid claims for prostate cancer agents at these health plans. By far, Lupron/Eligard represent the highest number of claims per 1 million member lives at 657, representing a cost of $1.17 million per 1 million member lives. How does your plan data compare? Prostate Cancer Claims – Benchmarks per 1 Million Lives Procedure Code Drug Name Description Allowed Amt./1 M Lives Units/1 M Lives Claims/1 M Lives Cost per Claim (allowed/ claims) Avg. Units (units/ claims) Dose per Claim J9217 Eligard/Lupron Leuprolide acetate (for depot suspension), 7.5 mg $1,166,485.36 2,059 657 $1,819.74 3 22.5 mg J9170 Taxotere Injection, docetaxel, 20 mg (code deleted effective 1/1/10 – see J9171) $217,933.71 554 124 $1,750.62 4 80 mg J3487 Zometa Injection, zoledronic acid (Zometa), 1 mg $143,477.64 575 172 $834.72 3 3 mg J9225 Vantas Histrelin implant (Vantas), 50 mg $131,402.42 34 35 $4,120.06 1 50 mg J3315 Trelstar Depot Injection, triptorelin pamoate, 3.75 mg $85,270.23 215 91 $1,035.73 2 7.5 mg J9202 Zoladex Goserelin acetate implant, per 3.6 mg $55,121.86 130 63 $784.81 2 7.2 mg J9045 Carboplatin Injection, carboplatin, 50 mg $15,438.27 104 20 $675.88 5 250 mg J9293 Novantrone Injection, mitoxantrone hydrochloride, per 5 mg $13,370.13 45 13 $1,373.59 4 20 mg J9265 Taxol Injection, paclitaxel, 30 mg $13,112.39 76 20 $588.09 3 90 mg Total spend for prostate cancer: Unique patients/1 million lives: $2,272,597.50 $571.65 Source: ICORE Healthcare Data Source, two regional health plans with more than 5 million lives, 12 months ending May 2009 What challenges do payors and providers face? We invite you to e-mail your ideas, comments, and questions to: [email protected] 10 managedcareoncology Quarter 1 2010 The incidence of CINV following moderately emetogenic chemotherapy (MEC) is often underestimated. The importance of prevention never should be. ALOXI provided significantly higher Complete Response (CR) in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) vs ondansetron Complete Response in a noninferiority trial1† (No emetic episode and no use of rescue medication) ALOXI 0.25 mg (n=189)‡ % of patients achieving CR 90 80 * 81.0 Ondansetron 32 mg (n=185)‡ 68.6 70 * 74.1 * 69.3 55.1 60 50 50.3 40 30 20 10 0 0-24 hours § (Acute) p =0.0085 24-120 hours (Delayed) p <0.001 0-120 hours (Overall) p <0.001 * p≤0.025 (adjusted post-hoc, 2-sided, Fisher’s exact test comparisons of ALOXI with ondansetron; 97.5% confidence interval [CI]). † Double-blind, randomized, Phase III noninferiority trial comparing single doses of ALOXI with ondansetron following MEC with a primary endpoint of CR. ‡ Intent-to-treat (ITT) cohort. § Clinical superiority over other 5-HT3 receptor antagonists has not been adequately demonstrated in the acute phase. Phase More than 10 million doses sold for prevention of CINV2 Indication —IMS Data 9/03-6/09 ALOXI® (palonosetron HCl) injection 0.25 mg is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy, and acute nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy. Important Safety Information • ALOXI is contraindicated in patients known to have hypersensitivity to the drug or any of its components • Most commonly reported adverse reactions in chemotherapy-induced nausea and vomiting include headache (9%) and constipation (5%) Please see the brief summary of prescribing information on the following page. References: 1. Gralla R, Lichinitser M, Van der Vegt S, et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003;14:1570-1577. 2. Data on file. Eisai Inc., Woodcliff Lake, NJ. ALOXI® is a registered trademark of Helsinn Healthcare SA, Switzerland, used under license. Distributed and marketed by Eisai Inc. © 2010 Eisai Inc. All rights reserved. Printed in USA. AL507 02/10 www.ALOXI.com ALOXI® (palonosetron HCl) injection BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE Chemotherapy-Induced Nausea and Vomiting ALOXI is indicated for: • Moderately emetogenic cancer chemotherapy – prevention of acute and delayed nausea and vomiting associated with initial and repeat courses • Highly emetogenic cancer chemotherapy – prevention of acute nausea and vomiting associated with initial and repeat courses DOSAGE AND ADMINISTRATION Recommended Dosing Chemotherapy-Induced Nausea and Vomiting Dosage for Adults - a single 0.25 mg I.V. dose administered over 30 seconds. Dosing should occur approximately 30 minutes before the start of chemotherapy. Instructions for I.V. Administration ALOXI is supplied ready for intravenous injection. ALOXI should not be mixed with other drugs. Flush the infusion line with normal saline before and after administration of ALOXI. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever solution and container permit. CONTRAINDICATIONS ALOXI is contraindicated in patients known to have hypersensitivity to the drug or any of its components. [see Adverse Reactions (6) in full prescribing information] WARNINGS AND PRECAUTIONS Hypersensitivity Hypersensitivity reactions may occur in patients who have exhibited hypersensitivity to other 5-HT3 receptor antagonists. ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates reported in practice. In clinical trials for the prevention of nausea and vomiting induced by moderately or highly emetogenic chemotherapy, 1374 adult patients received palonosetron. Adverse reactions were similar in frequency and severity with ALOXI and ondansetron or dolasetron. Following is a listing of all adverse reactions reported by ≥ 2% of patients in these trials (Table 1). Table 1: Adverse Reactions from ChemotherapyInduced Nausea and Vomiting Studies ≥ 2% in any Treatment Group ALOXI Ondansetron Dolasetron Event 0.25 mg 32 mg I.V. 100 mg I.V. (N=410) (N=633) (N=194) Headache 60 (9%) 34 (8%) 32 (16%) Constipation 29 (5%) 8 (2%) 12 (6%) Diarrhea 8 (1%) 7 (2%) 4 (2%) Dizziness 8 (1%) 9 (2%) 4 (2%) Fatigue 3 (< 1%) 4 (1%) 4 (2%) Abdominal Pain 1 (< 1%) 2 (< 1%) 3 (2%) Insomnia 1 (< 1%) 3 (1%) 3 (2%) In other studies, 2 subjects experienced severe constipation following a single palonosetron dose of approximately 0.75 mg, three times the recommended dose. One patient received a 10 mcg/kg oral dose in a postoperative nausea and vomiting study and one healthy subject received a 0.75 mg I.V. dose in a pharmacokinetic study. In clinical trials, the following infrequently reported adverse reactions, assessed by investigators as treatment-related or causality unknown, occurred following administration of ALOXI to adult patients receiving concomitant cancer chemotherapy: Cardiovascular: 1%: non-sustained tachycardia, bradycardia, hypotension, < 1%: hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation. In many cases, the relationship to ALOXI was unclear. Dermatological: < 1%: allergic dermatitis, rash. Hearing and Vision: < 1%: motion sickness, tinnitus, eye irritation and amblyopia. Gastrointestinal System: 1%: diarrhea, < 1%: dyspepsia, abdominal pain, dry mouth, hiccups and flatulence. General: 1%: weakness, < 1%: fatigue, fever, hot flash, flu-like syndrome. Liver: < 1%: transient, asymptomatic increases in AST and/or ALT and bilirubin. These changes occurred predominantly in patients receiving highly emetogenic chemotherapy. Metabolic: 1%: hyperkalemia, < 1%: electrolyte fluctuations, hyperglycemia, metabolic acidosis, glycosuria, appetite decrease, anorexia. Musculoskeletal: < 1%: arthralgia. Nervous System: 1%: dizziness, < 1%: somnolence, insomnia, hypersomnia, paresthesia. Psychiatric: 1%: anxiety, < 1%: euphoric mood. Urinary System: < 1%: urinary retention. Vascular: < 1%: vein discoloration, vein distention. Postmarketing Experience The following adverse reactions have been identified during postapproval use of ALOXI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Very rare cases (<1/10,000) of hypersensitivity reactions and injection site reactions (burning, induration, discomfort and pain) were reported from postmarketing experience of ALOXI 0.25 mg in the prevention of chemotherapy-induced nausea and vomiting. DRUG INTERACTIONS Palonosetron is eliminated from the body through both renal excretion and metabolic pathways with the latter mediated via multiple CYP enzymes. Further in vitro studies indicated that palonosetron is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6, or CYP3A4/5. Therefore, the potential for clinically significant drug interactions with palonosetron appears to be low. Coadministration of 0.25 mg I.V. palonosetron and 20 mg I.V. dexamethasone in healthy subjects revealed no pharmacokinetic drug-interactions between palonosetron and dexamethasone. In an interaction study in healthy subjects where palonosetron 0.25 mg (I.V. bolus) was administered on day 1 and oral aprepitant for 3 days (125 mg/80 mg/80 mg), the pharmacokinetics of palonosetron were not significantly altered (AUC: no change, Cmax: 15% increase). A study in healthy volunteers involving single-dose I.V. palonosetron (0.75 mg) and steady state oral metoclopramide (10 mg four times daily) demonstrated no significant pharmacokinetic interaction. In controlled clinical trials, ALOXI injection has been safely administered with corticosteroids, analgesics, antiemetics/antinauseants, antispasmodics and anticholinergic agents. Palonosetron did not inhibit the antitumor activity of the five chemotherapeutic agents tested (cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C) in murine tumor models. USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects: Category B Teratology studies have been performed in rats at oral doses up to 60 mg/kg/day (1894 times the recommended human intravenous dose based on body surface area) and rabbits at oral doses up to 60 mg/ kg/day (3789 times the recommended human intravenous dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to palonosetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, palonosetron should be used during pregnancy only if clearly needed. Labor and Delivery Palonosetron has not been administered to patients undergoing labor and delivery, so its effects on the mother or child are unknown. Nursing Mothers It is not known whether palonosetron is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants and the potential for tumorigenicity shown for palonosetron in the rat carcinogenicity study, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness in patients below the age of 18 years have not been established. Geriatric Use Population pharmacokinetics analysis did not reveal any differences in palonosetron pharmacokinetics between cancer patients ≥ 65 years of age and younger patients (18 to 64 years). Of the 1374 adult cancer patients in clinical studies of palonosetron, 316 (23%) were ≥ 65 years old, while 71 (5%) were ≥ 75 years old. No overall differences in safety or effectiveness were observed between these subjects and the younger subjects, but greater sensitivity in some older individuals cannot be ruled out. No dose adjustment or special monitoring are required for geriatric patients. Of the 1520 adult patients in ALOXI PONV clinical studies, 73 (5%) were ≥65 years old. No overall differences in safety were observed between older and younger subjects in these studies, though the possibility of heightened sensitivity in some older individuals cannot be excluded. No differences in efficacy were observed in geriatric patients for the CINV indication and none are expected for geriatric PONV patients. However, ALOXI efficacy in geriatric patients has not been adequately evaluated. Renal Impairment Mild to moderate renal impairment does not significantly affect palonosetron pharmacokinetic parameters. Total systemic exposure increased by approximately 28% in severe renal impairment relative to healthy subjects. Dosage adjustment is not necessary in patients with any degree of renal impairment. Hepatic Impairment Hepatic impairment does not significantly affect total body clearance of palonosetron compared to the healthy subjects. Dosage adjustment is not necessary in patients with any degree of hepatic impairment. Race Intravenous palonosetron pharmacokinetics was characterized in twenty-four healthy Japanese subjects over the dose range of 3 – 90 mcg/kg. Total body clearance was 25% higher in Japanese subjects compared to Whites, however, no dose adjustment is required. The pharmacokinetics of palonosetron in Blacks has not been adequately characterized. OVERDOSAGE There is no known antidote to ALOXI. Overdose should be managed with supportive care. Fifty adult cancer patients were administered palonosetron at a dose of 90 mcg/kg (equivalent to 6 mg fixed dose) as part of a dose ranging study. This is approximately 25 times the recommended dose of 0.25 mg. This dose group had a similar incidence of adverse events compared to the other dose groups and no dose response effects were observed. Dialysis studies have not been performed, however, due to the large volume of distribution, dialysis is unlikely to be an effective treatment for palonosetron overdose. A single intravenous dose of palonosetron at 30 mg/kg (947 and 474 times the human dose for rats and mice, respectively, based on body surface area) was lethal to rats and mice. The major signs of toxicity were convulsions, gasping, pallor, cyanosis and collapse. PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (17.2) in full prescribing information Instructions for Patients • Patients should be advised to report to their physician all of their medical conditions, any pain, redness, or swelling in and around the infusion site [see Adverse Reactions (6) in full prescribing information]. • Patients should be instructed to read the patient insert. Rx Only Mfd by OSO Biopharmaceuticals, LLC, Albuquerque, NM, USA or Pierre Fabre, Médicament Production, Idron, Aquitaine, France and Helsinn Birex Pharmaceuticals, Dublin, Ireland. ALOXI® is a registered trademark of Helsinn Healthcare SA, Switzerland, used under license. Distributed and marketed by Eisai Inc., Woodcliff Lake, NJ 07677. © 2009 Eisai Inc. All rights reserved. Printed in USA. AL449 08/09 industry thought leaders A Discussion with Gary J. Tereso PharmD, Manager of Pharmacy Services, Health New England, Inc. As the first health plan in the country to undergo accreditation review by the National Committee for Quality Assurance (NCQA), Health New England, Inc. (HNE) has long been on the forefront of healthcare quality improvement. Gary J. Tereso, PharmD HNE currently enjoys an Excellent accreditation status from NCQA. According to the NCQA’s Quality Compass 2009, HNE achieved the highest rating among Massachusetts commercial HMO/POS health plans in the Consumer Assessment of Healthcare Providers and Systems (CAHPS) member satisfaction survey measures for Customer Service, Claims Processing, and Plan Information on Cost. HNE is currently ranked eighth in the country out of 239 commercial health plans by U.S. News & World Report and the NCQA. Managed Care Oncology recently sat down with Gary J. Tereso, PharmD, Manager of Pharmacy Services, to gain his insights on high-quality, costeffective care in the oncology specialty. MCO: How do you see some of the current proposed healthcare reforms affecting cancer care at your health plan? Dr. Tereso: What makes healthcare reform a challenge for us is the level of uncertainty that’s currently out there. Recently, there have been some changes in policy that have made the future very difficult to predict. Plans in Massachusetts are in a unique situation because, in addition to federal regulations, we must follow state insurance regulations that are perhaps the most far-reaching in the country. For example, state regulations dictate that we need to cover a large majority of cancer treatments even if they have not been approved by the U.S. Food and Drug Administration. Massachusetts in general has been held to a higher standard. No matter what transpires with healthcare reform, we’re going to have to continue to monitor therapies for appropriateness and effectiveness. MCO: What strategies are you currently considering or implementing to prepare for the future? Dr. Tereso: One of the strategies that we’ve already put in place is the evaluation of certain medication fee schedules. Approximately three years ago, we implemented ICORE’s variable fee schedule, which allows for improved reimbursement for certain injectable medications that are most appropriate to treat the patient. The thinking behind this initiative was to rationalize the reimbursement methodology. This fee schedule also eliminates the possibility of providers using therapies to generate large amounts of revenue associated with costly therapies. Of course, the fee schedule is always evolving, and we’ll continue to modify it as time goes on. The ultimate goal is to control premiums so that everyone is able to managedcareoncology.com 13 have healthcare – Massachusetts was one of the first states to enact legislation mandating all residents carry insurance. Another strategy that began several years ago was to integrate all the clinical areas – including behavioral health, case management, disease management, health programs, and pharmacy services – to eliminate the “silo effect” and look at the whole member. We are now known as the clinical service integration team, and decisions on how to address complex member issues are made by a team of individuals with different clinical backgrounds – such as licensed independent clinical social workers, physicians, pharmacists, and registered nurses – instead of by one department. Also, in an effort to remain current and knowledgeable in oncology, for several years we’ve been hiring certain specialists working in the field. For example, we recently hired a pharmacist who is board certified in oncology. The ever-changing dynamics of oncology and the complexities of the various treatment regimens made us realize that we needed to have an internal expert on staff who specializes in this field. MCO: What do you see as some of the major cancer treatment challenges facing health plans in the next few years? Dr. Tereso: The most apparent challenge related to cancer treatment in general is the high cost associated with some of the new therapies. Annualized, these therapies may cost upward of $50,000 to $100,000 per year. Responding thoughtfully to these therapies requires an approach that preserves access to appropriate treatment while assuming that premium costs do not outpace consumers’ ability to afford coverage. Another challenge, specifically related to prostate cancer, is the increasing complexity of treatment regimens and the treatment variation that accompanies the introduction of new therapies. Whereas there was originally only one medication used in the treatment of this disease, oncologists now have multiple options for therapy. Also, prostate cancer is often treated with relatively costly and long-term regimens, so when you consider that prostate cancer is the second-leading type of nonskin cancer, the sheer numbers make it difficult to manage. Because of the regularity and frequency with which prostate cancer is diagnosed, treatment of this disease is high on our radar screen. The balance between cancer therapy and treatment outcomes is likewise a big challenge for health plans. While there have been advances in cancer therapy in recent years, some people may see the related treatment outcomes as being incremental. Still, despite some therapies being viewed as having incremental clinical benefits, everyone wants to have access to them. This makes it difficult for health plans attempting to manage utilization and appropriateness, since they are often seen as being insensitive for limiting access to certain therapies. MCO: How can health plans and providers better work together to ensure high-quality cancer care that doesn’t drive costs out of control? Dr. Tereso: First and foremost, communication needs to be improved so that the health plan and the providers – two groups that both play important roles in managing the overall member – have access to much of the same information. Health plans have an extensive amount of useful 14 managedcareoncology Quarter 1 2010 data at their fingertips that providers don’t have access to – care at other sites of service, drugs prescribed by other specialists, even whether some diagnostic studies have been performed; these data need to be shared with the providers so that they may offer the most appropriate care. On the other hand, providers also have information of which the health plan may not be aware – such as lab values, tumor stage, or functional status. As such, anything providers can do in the way of presenting this type of information, which might be preventing an approval or limiting the availability of a specific regimen, would benefit the overall provision of cost-effective care to the member. Also, health plans and providers need to come to some sort of agreement on reimbursement. Specifically, plans want to reimburse providers for services rendered instead of medication costs. Providers do so, as well, but payors and providers alike struggle with how this transition is managed. legislation being passed on costeffective therapy. Such legislation and a number of other factors should bring the management of chemotherapy cost to the forefront and allow for certain comparisons to be drawn between therapies. For example, in terms of prostate cancer treatment, the different luteinizing hormonereleasing hormone agonists have only been evaluated in placebo-controlled trials to date. However, as healthcare costs continue to rise and plans demand data that will allow them to differentiate between therapies, comparative trials are planned for the future. MCO: Are you considering any initiatives around end-of-life treatment decisions for terminally ill cancer patients? MCO: How important is survival and outcomes data to the management of chemotherapy cost? Dr. Tereso: Survival and outcomes data are extremely important in the management of chemotherapy cost. Ultimately, the most important thing to HNE is its members and its members’ overall health. The plan is there to help them and assist them in navigating their healthcare treatment. This is a particular challenge with respect to chemotherapy. Some of the survival and outcomes data in oncology are incremental in comparison to those seen in other disease states. Even though these data components are extremely important, it’s difficult to draw comparisons with other disease states when initially evaluating the information. The importance of managing chemotherapy cost is going to be increasingly high on the radar screen of health plans, especially with Dr. Tereso: Unfortunately, for some members, the topic of hospice is one that seems to occur late. Hospice is meant to improve the extensive period of end-of-life care and make it as palliative as possible; however, many providers are using it only at the very end of life – that is, 24 to 48 hours before the patient passes on. Conversely, our members are generally directed to hospice care at an earlier stage, which we believe is appropriate. There are also certain therapies that are used in end-of-life situations that haven’t been studied in this setting. This is an area from a benefit perspective that could use some re-evaluating. MCO: Some plans are considering disease- and case-management programs for the care of cancer. Are you implementing any similar initiatives at HNE? Dr. Tereso: We’re currently in the process of developing an oncology/ pain disease management program. Considering the complexities involved in the treatment of cancer, where there are medical breakthroughs on a daily basis, it’s a challenge for anyone to keep up. The disease management program, headed up by our oncology pharmacist, is designed to address this concern. Once the program is up and running, we’ll be doing claims analyses to recognize trends within the provider network for cancer therapy in general. What makes this such a high area of concern is the variability in how diseases are managed and dollars are spent. You may see one provider utilizing one regimen, while a different provider utilizes a completely different regimen. National guidelines such as the National Comprehensive Cancer Network’s (NCCN) Clinical Practice Guidelines in Oncology™ have made this area much clearer, although there are still a myriad of different treatment choices within each cancer type. Our disease management program will not dictate that only one specific therapy be used but rather document which therapies are acceptable in accordance with the NCCN. In general, there aren’t many resources and analyses to say that one specific regimen is better than all the others in one specific situation. In fact, aside from some of the newer genetic markers that help clarify who should be treated with a specific therapy, cancer treatment overall still has a long way to go. At HNE, we’re trying to encourage matching appropriate therapies with appropriate members. In doing so, we try to consider all relevant factors: cost, outcomes, survival data, and the best interests of our members. managedcareoncology.com 15 pipeline report Investigational Agents for the Treatment of Prostate Cancer by Howard “Skip” Burris, MD, Director of Drug Development, The Sarah Cannon Research Institute Prostate cancer continues to be a global health issue with more than 700,000 men diagnosed worldwide every year, including more than 200,000 in the U.S. Unfortunately, despite early detection and improved treatment, more than 25,000 men will die of prostate cancer in the U.S. this year. Metastases to the bone occur in more than 90% of advanced prostate cancer patients and approximately 40% experience softtissue lesions. 16 managedcareoncology Quarter 1 2010 Prostate cancer is hormone-sensitive at the time of initial diagnosis. Most advanced-disease patients respond to conventional androgen deprivation with castration, either medical or surgical. The duration of disease control with castration is 18 to 24 months with an overall survival of 30 to 36 months. The terms hormone-refractory prostate cancer (HRPC) and androgen-independent prostate cancer (AIPC) are commonly used to describe patients whose disease progresses after castration. There are several new agents in development to treat prostate cancer resistant to initial castration. In the castrate state, ligands to the androgen receptor are derived predominantly from the adrenal glands. Approximately 10% of circulating testosterone remains after androgendeprivation therapy due to the peripheral conversion of adrenal steroids. The need to suppress androgen production in the adrenal glands and at tissue levels persists in HRPC/AIPC. Chemotherapeutic docetaxel has received U.S. Food and Drug Administration (FDA) approval for improving survival in HRPC patients, although that benefit has been modest. No second-line hormonal therapies have been FDAapproved as their efficacies have been limited. Abiraterone (CB7598) is a steroidal irreversible inhibitor of CYP17 (17 alpha hydroxylase/17, 20 lyase), thus blocking two important enzymatic activities in the synthesis of testosterone. Abiraterone acetate (CB7630) is a prodrug of abiraterone and is rapidly converted after oral administration. Activity was seen in phase 1 and 2 trials as manifested by both durable prostate-specific antigen (PSA) declines and objective responses. Side effects have included hypertension, hypokalemia, and lower extremity edema, all consistent with abiraterone’s mechanism of action. Doses explored ranged from 250 mg to 2,000 mg, and 1,000 mg has been selected for a phase 2 trial after demonstrating consistent pharmacologic effects without additional side effects. Abiraterone’s results in 52 chemotherapy-naive HRPC patients reveal more than 60% of patients with PSA declines of more than 50% and 25% with declines of more than 90%. Objective responses were documented in 12 of 21 patients. In the postchemotherapy (docetaxel) group, two phase 2 studies have been conducted with one-half of the patients achieving a greater than 50% PSA decline lasting a median of 24 weeks. A randomized phase 3, doubleblind, placebo-controlled study of abiraterone/prednisone vs. placebo/ prednisone (2:1) in more than 800 patients has recently finished accrual. A similar phase 3 trial in patients not thought to need chemotherapy yet is in the midst of accrual. Another compound, MDV3100, is a novel small-molecule androgen receptor that binds more tightly to the androgen receptor (AR) than bicalutamide. Unlike bicalutamide, MDV3100 inhibits AR function by blocking nuclear translocation of the AR and DNA binding. To date, 140 HRPC patients have been treated with MDV3100. The initial results are encouraging with PSA declines of more than 50% documented in 62% of chemotherapy-naive patients and 51% of chemotherapy-treated patients, with median time to progression in excess of 200 days for both groups. A dose of 240 mg per day is the maximum tolerated dose, and the most common toxicity is fatigue. A phase 3 randomized 2:1, double-blind, placebo-controlled trial of MDV3100 at 160 mg per day vs. placebo in more than 1,000 patients is under way. Also in this class of innovative hormone therapies is TAK-700, an orally managedcareoncology.com 17 active, potent nonsteroidal inhibitor of 17, 20 lyase. Initial phase 1/2 safety and efficacy trials are under way in prostate cancer. The addition of biologic therapy to chemotherapy remains of interest. Studies of bevacizumab and docetaxel in high-risk, neoadjuvant prostate patients reveal encouraging activity. Magnetic resonance imaging of the prostate showed median tumor size decreases of 45%; 39% of patients were considered to have partial responses (PRs). AT-101 is an oral pan-Bcl-2 inhibitor with single-agent activity in HRPC. When given in combination with docetaxel and prednisone, 24 of 36 patients met PR criteria with a more than 50% decline in PSA. In addition, nine of 19 patients with measurable disease had PRs per Response Evaluation Criteria in Solid Tumors (RECIST). Phase 3 studies of the combination are now under way. The anti-interleukin (IL)-6 monoclonal antibody CNT0328 has been studied with docetaxel, and more than 50% of patients had responses by PSA; plus three of 12 patients with measurable disease had PRs. Fatigue was the predominant toxicity attributed to the combination. Several chemotherapeutics are being evaluated in docetaxel-resistant HRPC, specifically the epothilones. Ixabepilone and sagopilone are two agents in this class with demonstrated phase 2 activity manifested by both PSA declines and soft-tissue shrinkage. Further trials are under way to explore the advantages of these agents, which are less affected by the multidrug resistance cellular pumps. A novel approach to the treatment of advanced prostate cancer is being developed by Dendreon Corporation, a Seattle biotechnology company. Dendreon has filed for FDA approval of the first so-called therapeutic cancer vaccine, Provenge. Provenge does not aim to prevent disease like childhood vaccines. Instead, Provenge is designed to train the body’s immune system to attack the cancer once the patient has already developed the disease. Provenge is produced by taking cells from a patient’s tumor, incorporating them into an individualized vaccine, then returning them to a physician to be injected back into the patient. Active treatment consists of three injections of Provenge given over the course of one month. Investigators reported last April that in a phase 3 study of 512 patients with advanced prostate cancer, Provenge extended survival by 4.1 months. The most common side effects were flulike symptoms for a day or two after treatment, less harsh than those from chemotherapy. A decision on the FDA approval is expected in the first half of 2010. Supportive care for the prostate patient must be remembered. The bisphosphonates have been shown to decrease fractures and improve bone health. Denosumab, a fully human monoclonal antibody against RANK ligand, improves bone mineral density and decreases fractures. Placebo-controlled studies and evaluations in comparison to bisphosphonates are under way. References 1. Scher HI, Beer TM, Higano CS, et al. Antitumor activity of MDV3100 in a phase 1/2 study of castration-resistant prostate cancer (CRPC). Proc Am Soc Clin Oncol. 2009;27:237s [abstract #5011]. 2. Oh WK, Febbo PG, Richie JP, et al. A phase 2 study of neoadjuvant chemotherapy with docetaxel and bevacizumab in patients (pts) with high-risk localized prostate cancer: a Prostate Cancer Clinical Trials Consortium trial. Proc Am Soc Clin Oncol. 2009;27:249s [abstract #5060]. 3. MacVicar GR, Greco A, Reeves J, et al. An open-label, multicenter, phase 1/2 study of AT-101 in combination with docetaxel (D) and prednisone (P) in men with castrate-resistant prostate cancer (CRPC). Proc Am Soc Clin Oncol. 2009;27:249s [abstract #5062]. 4. Hudes G, Tagawa S, Whang Y, et al. A phase 1 study of CNT0328, an anti-interleukin (IL)-6 monoclonal antibody combined with docetaxel in subjects with metastatic castration-resistant prostate cancer (CRPC). Proc Am Soc Clin Oncol. 2009;27:249s [abstract #5063]. 5. Saad F, Smith MR, Egerdie B, et al. Denosumab for prevention of fractures in men receiving androgen deprivation therapy (ADT) for prostate cancer (PC). Proc Am Soc Clin Oncol. 2009;27:248s [abstract #5056]. 6. Small E, Harzstark A, Weinberg VK. Ixabepilone, mitoxantrone, and prednisone in patients with metastatic castrationresistant prostate cancer refractory to docetaxel-based therapy: a phase 2 study of the DOD Prostate Cancer Clinical Trials Consortium. Proc Am Soc Clin Oncol. 2009;27:248s [abstract #5058]. 7. Beer TM, Smith DC, Hussain A, et al. Phase 2 study of first-line sagopilone combined with prednisone in patients with metastatic castratrion-resistant prostate cancer (CRPC). Proc Am Soc Clin Oncol. 2009;27:248s [abstract #5059]. 8. Ryan C, Efstathiou E, Smith M. Phase 2 multicenter study of chemotherapy (chemo)-naive castration-resistant prostate cancer (CRPC) not exposed to ketoconazole (keto), treated with abiraterone acetate (AA) plus prednisone. Proc Am Soc Clin Oncol. 2009;27:245s [abstract #5046]. 9. Reid AH, Attard G, Danila D. A multicenter phase 2 study of abiraterone acetate (AA) in docetaxel pretreated castrationresistant prostate cancer (CRPC) patients (pts). Proc Am Soc Clin Oncol. 2009;27:246s [abstract #5047]. 18 managedcareoncology Quarter 1 2010 For previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens When planning a treatment course for DLBCL Take the essential path toward improved survival Cumulative Cumulative Proportion Proportion Surviving Surviving RITUXAN+CHOP is proven to prolong survival in DLBCL 47% INCREASE in 7-year OS in GELA* trial 1,2 1.0 0.8 0.6 0.4 R-CHOP (n=202) CHOP† (n=197) p =0.0004 0.2 0 0 Years 1 2 3 4 5 6 7 8 • At 7 years, 8 cycles of RITUXAN+ CHOP increased overall survival (OS) from 36% to 53% compared with CHOP alone1 • At 5 years, 8 cycles of RITUXAN+ CHOP increased OS from 46% to 58% compared with CHOP alone 5 BOXED WARNINGS and Additional Important Safety Information The most important serious adverse reactions of RITUXAN are fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B reactivation with fulminant hepatitis, other viral infections, cardiovascular events, renal toxicity, and bowel obstruction and perforation. The most common adverse reactions of RITUXAN (incidence ≥25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia.5 RITUXAN in Combination with CHOP Chemotherapy for DLBCL: The following adverse reactions, regardless of severity, were reported more frequently (≥5%) in patients age ≥60 years receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs 46%), lung disorder (31% vs 24%), cardiac disorder (29% vs 21%), and chills (13% vs 4%). In the GELA LNH 98-5 study, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs 1.0% for CHOP).5 The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs 7%) and lung disorder (6% vs 3%). Other Grade 3 or 4 adverse reactions reported more frequently among patients receiving R-CHOP were viral infection (GELA LNH 98-5 study), neutropenia (GELA LNH 98-5 and MInT studies), and anemia (MInT study).5 Please see brief summary of prescribing information on adjacent page. Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion. *GELA (Groupe d’Etude des Lymphomes de l’Adulte) LNH 98-5 trial: A Phase III trial of 399 previously untreated elderly (age ≥60 years) DLBCL patients.3,4 †CHOP: Cyclophosphamide, doxorubicin, vincristine, and prednisone. References: 1. Coiffier B, Feugier P, Mounier N, et al. Long-term results of the GELA study comparing R-CHOP and CHOP chemotherapy in older patients with diffuse large B-cell lymphoma show good survival in poor-risk patients. J Clin Oncol. 2007;25(suppl 18S):443s. Abstract 8009. 2. Coiffier B, Feugier P, Mounier N, et al. Long-term results of the GELA study comparing R-CHOP and CHOP chemotherapy in older patients with diffuse large B-cell lymphoma show good survival in poor-risk patients. Paper presented at: 43rd American Society of Clinical Oncology Annual Meeting; June 1-5, 2007; Chicago, Ill. Abstract 8009. 3. Coiffier B, Lepage E, Brière J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse largeB-cell lymphoma. N Engl J Med. 2002;346:235-242. 4. Data on file, Genentech, Inc. 5. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2008. PROVE N. POWE R FU L. ©2008 Genentech, Inc., and Biogen Idec Inc. All rights reserved. 3 Printed in USA on Recycled Paper 8957001 April 2008 RITUXAN® (Rituximab) Brief summary—Please consult full prescribing information. WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) Infusion Reactions: Rituxan administration can result in serious, including fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Carefully monitor patients during infusions. Discontinue Rituxan infusion and provide medical treatment for Grade 3 or 4 infusion reactions [see Warnings and Precautions, Adverse Reactions]. Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non-Hodgkin’s lymphoma (NHL) patients with Rituxan [see Warnings and Precautions, Adverse Reactions]. Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan [see Warnings and Precautions, Adverse Reactions]. Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving Rituxan [see Warnings and Precautions, Adverse Reactions]. INDICATIONS AND USAGE Non-Hodgkin’s Lymphoma (NHL) Rituxan® (rituximab) is indicated for the treatment of patients with: Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent; Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy; Non-progressing (including stable disease), low-grade, CD20positive B-cell NHL, as a single agent, after first-line CVP chemotherapy; Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens. WARNINGS AND PRECAUTIONS Infusion Reactions Rituxan can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion with time to onset of 30–120 minutes. Rituxan-induced infusion reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, or anaphylactoid events. Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g., glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion reactions as needed. Depending on the severity of the infusion reaction and the required interventions, consider resumption of the infusion at a minimum 50% reduction in rate after symptoms have resolved. Closely monitor the following patients: those with preexisting cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (≥25,000/mm3). [See Boxed Warning, Warnings and Precautions, Adverse Reactions.] Tumor Lysis Syndrome (TLS) Rapid reduction in tumor volume followed by acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia, can occur within 12–24 hours after the first infusion. Fatal TLS cases have occurred after administration of Rituxan. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burden confers a greater risk of TLS after rituximab. Consider prophylaxis for TLS in patients at high risk. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated. [See Boxed Warning.] Severe Mucocutaneous Reactions Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with Rituxan. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these reactions has varied from 1–13 weeks following Rituxan exposure. Discontinue Rituxan in patients who experience a severe mucocutaneous reaction. The safety of readministration of Rituxan to patients with severe mucocutaneous reactions has not been determined. [See Boxed Warning, Adverse Reactions.] Progressive Multifocal Leukoencephalopathy (PML) JC virus infection resulting in PML and death can occur in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases. The majority of patients with hematologic malignancies diagnosed with PML received Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell transplant. The patients with autoimmune diseases had prior or concurrent immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of their last infusion of Rituxan. Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations. Discontinue Rituxan and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. [See Boxed Warning, Adverse Reactions.] Hepatitis B Virus (HBV) Reactivation Hepatitis B Virus (HBV) reactivation with fulminant hepatitis, hepatic failure, and death can occur in patients with hematologic malignancies treated with Rituxan. The median time to the diagnosis of hepatitis was approximately 4 months after the initiation of Rituxan and approximately one month after the last dose. Screen patients at high risk of HBV infection before initiation of Rituxan. Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV infection for several months following Rituxan therapy. Discontinue Rituxan and any concomitant chemotherapy in patients who develop viral hepatitis, and institute appropriate treatment including antiviral therapy. Insufficient data exist regarding the safety of resuming Rituxan in patients who develop hepatitis subsequent to HBV reactivation. [See Adverse Reactions.] Other Viral Infections The following additional serious viral infections, either new, reactivated, or exacerbated, have been identified in clinical studies or postmarketing reports. The majority of patients received Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell transplant. These viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis C. In some cases, the viral infections occurred as late as one year following discontinuation of Rituxan and have resulted in death. [See Adverse Reactions.] Cardiovascular Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of Rituxan for patients who develop clinically significant arrhythmias or who have a history of arrhythmia or angina. [See Adverse Reactions.] Renal Severe, including fatal, renal toxicity can occur after Rituxan administration in patients with hematologic malignancies. Renal toxicity has occurred in patients with high numbers of circulating malignant cells (≥25,000/mm3) or high tumor burden who experience tumor lysis syndrome and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and Rituxan is not an approved treatment regimen. Use extreme caution if this non-approved combination is used in clinical trials and monitor closely for signs of renal failure. Consider discontinuation of Rituxan for patients with a rising serum creatinine or oliguria. Bowel Obstruction and Perforation Abdominal pain, bowel obstruction and perforation, in some Chemotherapy for DLBCL In Studies 6 and 7, the following adverse reactions, regardless of severity, were reported more frequently (≥5%) in patients age ≥60 years receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs. 46%), lung disorder (31% vs. 24%), cardiac disorder (29% vs. 21%), and chills (13% vs. 4%). Detailed safety data collection in these studies was primarily limited to Grade 3 and 4 adverse reactions and serious adverse reactions. In Study 7, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs. 1.0% for CHOP). The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs. 7%) and lung disorder (6% vs. 3%). Other Grade 3 or 4 adverse reactions occurring more frequently among patients receiving R-CHOP were viral infection (Study 7), neutropenia (Studies 7 and 8), and anemia (Study 8). Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Rituxan with the incidence of antibodies to other products may be misleading. Using an ELISA assay, antihuman anti-chimeric antibody (HACA) was detected in 4 of 356 (1.1%) patients with low-grade or follicular NHL receiving single-agent Rituxan. Three of the four patients had an objective clinical response. The clinical relevance of HACA formation in rituximab treated patients is unclear. Postmarketing Experience The following adverse reactions have been identified during postapproval use of Rituxan in hematologic malignancies. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Rituxan. Hematologic: prolonged pancytopenia, marrow hypoplasia, and late-onset neutropenia, hyperviscosity syndrome in Waldenstrom’s macroglobulinemia. Cardiac: fatal cardiac failure. Immune/Autoimmune Events: uveitis, optic neuritis, systemic vasculitis, pleuritis, lupus-like syndrome, serum sickness, polyarticular arthritis, and vasculitis with rash. Infection: viral infections, including progressive multifocal leukoencephalopathy (PML), increase in fatal infections in HIV-associated lymphoma, and a reported increased incidence of Grade 3 and 4 infections in patients with previously treated lymphoma without known HIV infection. Neoplasia: disease progression of Kaposi’s sarcoma. Skin: severe mucocutaneous reactions. Gastrointestinal: bowel obstruction and perforation. Pulmonary: fatal bronchiolitis obliterans and pneumonitis (including interstitial pneumonitis). DRUG INTERACTIONS Formal drug interaction studies have not been performed with Rituxan. USE IN SPECIFIC POPULATIONS Pregnancy Category C: There are no adequate and well-controlled studies of rituximab in pregnant women. Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than six months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero. Non-Hodgkin’s lymphoma is a serious condition that requires treatment. Rituximab should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Reproduction studies in cynomolgus monkeys at maternal exposures similar to human therapeutic exposures showed no evidence of teratogenic effects. However, B-cell lymphoid tissue was reduced in the offspring of treated dams. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months of birth. Nursing Mothers It is not known whether Rituxan is secreted into human milk. However, Rituxan is secreted in the milk of lactating cynomolgus monkeys, and IgG is excreted in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts. The unknown risks to the infant from oral ingestion of Rituxan should be weighed against the known benefits of breastfeeding. Pediatric Use The safety and effectiveness of Rituxan in pediatric patients have not been established. Geriatric Use Diffuse Large B-Cell NHL Among patients with DLBCL evaluated in three randomized, activecontrolled trials, 927 patients received Rituxan in combination with chemotherapy. Of these, 396 (43%) were age 65 or greater and 123 (13%) were age 75 or All Grades (%) Grade 3 and 4 (%) All Grades (%) Grade 3 and 4 (%) greater. No overall differences in effectiveness were observed between these Respiratory System Any Adverse Events 99 57 38 4 patients and younger patients. Cardiac adverse reactions, mostly supraventricular Body as a Whole Increased Cough 13 1 86 10 Rhinitis 12 1 Fever 53 1 arrhythmias, occurred more frequently among elderly patients. Serious pulmonary Bronchospasm 8 1 Chills 33 3 adverse reactions were also more common among the elderly, including Dyspnea 7 1 Infection 31 4 Sinusitis 6 0 Asthenia 26 1 pneumonia and pneumonitis. Low-Grade or Follicular Non-Hodgkin’s Metabolic and Nutritional Headache 19 1 Lymphoma Clinical studies of Rituxan in low-grade or follicular, CD20-positive, Abdominal Pain 14 1 Disorders 38 3 Pain 12 1 Angioedema 11 1 B-cell NHL did not include sufficient numbers of patients aged 65 and over to Back Pain 10 1 Hyperglycemia 9 1 Throat Irritation 9 0 Peripheral Edema 8 0 determine whether they respond differently from younger subjects. Flushing 5 0 LDH Increase 7 0 OVERDOSAGE There has been no experience with overdosage in human clinical Heme and Lymphatic System 67 Digestive System 48 37 2 Lymphopenia 48 40 Nausea 23 1 trials. Single doses of up to 500 mg/m2 have been given in dose-escalation Leukopenia 14 4 Diarrhea 10 1 Neutropenia 14 6 Vomiting 10 1 clinical trials. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Thrombocytopenia 12 2 Nervous System 32 1 Impairment of Fertility No long term animal studies have been performed to Anemia 8 3 Dizziness 10 1 Skin and Appendages Anxiety 5 1 44 2 establish the carcinogenic or mutagenic potential of Rituxan or to determine Musculoskeletal System Night Sweats 15 1 26 3 Rash 15 1 Myalgia 10 1 potential effects on fertility in males or females. PATIENT COUNSELING Pruritus 14 1 Arthralgia 10 1 INFORMATION Patients should be provided the Rituxan Medication Guide and Urticaria 8 1 Cardiovascular System 25 3 Hypotension 10 1 provided an opportunity to read prior to each treatment session. Because caution Hypertension 6 1 should be exercised in administering Rituxan to patients with active infections, it is a Adverse reactions observed up to 12 months following Rituxan. bAdverse reactions graded for severity by important that the patient’s overall health be assessed at each visit and any NCI-CTC criteria. questions resulting from the patient’s reading of the Medication Guide be In these single-arm Rituxan studies, bronchiolitis obliterans occurred during and discussed. Rituxan is detectable in serum for up to six months following up to 6 months after Rituxan infusion. Rituxan in Combination With completion of therapy. Individuals of childbearing potential should use effective Chemotherapy Adverse reactions information below is based on 1250 patients contraception during treatment and for 12 months after Rituxan therapy. who received Rituxan in combination with chemotherapy or following chemotherapy. Rituxan in Combination With Chemotherapy for Low-Grade NHL In Study 4, patients in the R-CVP arm experienced a higher incidence of infusional toxicity and neutropenia compared to patients in the CVP arm. The following adverse reactions occurred more frequently (≥5%) in patients receiving R-CVP compared to CVP alone: rash (17% vs. 5%), cough (15% vs. 6%), flushing (14% vs. 3%), rigors (10% vs. 2%), pruritus (10% vs. 1%), neutropenia (8% vs. 3%), and chest tightness (7% vs. 1%). In Study 5, the following adverse reactions Revised 9/2008 (4835505) were reported more frequently (≥5%) in patients receiving Rituxan following CVP Jointly Marketed by: compared to patients who received no further therapy: fatigue (39% vs. 14%), Biogen Idec Inc. 5200 Research Place San Diego, CA 92122 anemia (35% vs. 20%), peripheral sensory neuropathy (30% vs. 18%), infections Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990 (19% vs. 9%), pulmonary toxicity (18% vs. 10%), hepato-biliary toxicity (17% vs. 7%), rash and/or pruritus (17% vs. 5%), arthralgia (12% vs. 3%), and weight gain (11% vs. 4%). Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more frequently (≥2%) in the Rituxan arm compared with those who received no further therapy (4% vs. 1%). Rituxan in Combination With ©2008 Biogen Idec Inc. and Genentech, Inc. 7140917 October 2008 cases leading to death, can occur in patients receiving Rituxan in combination with chemotherapy. In postmarketing reports, the mean time to documented gastrointestinal perforation was 6 (range 1–77) days in patients with NHL. Perform a thorough diagnostic evaluation and institute appropriate treatment for complaints of abdominal pain, especially early in the course of Rituxan therapy. [See Adverse Reactions.] Immunization The safety of immunization with live viral vaccines following Rituxan therapy has not been studied and vaccination with live virus vaccines is not recommended. For NHL patients, the benefits of primary or booster vaccinations should be weighted against the risks of delay in initiation of Rituxan therapy. Laboratory Monitoring Because Rituxan binds to all CD20positive B lymphocytes (malignant and non-malignant), obtain complete blood counts (CBC) and platelet counts at regular intervals during Rituxan therapy and more frequently in patients who develop cytopenias [see Adverse Reactions]. The duration of cytopenias caused by Rituxan can extend months beyond the treatment period. ADVERSE REACTIONS The most common adverse reactions of Rituxan (incidence ≥25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia. The most important serious adverse reactions of Rituxan are infusion reactions, tumor lysis syndrome, mucocutaneous toxicities, hepatitis B reactivation with fulminant hepatitis, PML, other viral infections, cardiac arrhythmias, renal toxicity, and bowel obstruction and perforation. Clinical Trials Experience Non-Hodgkin’s Lymphoma Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to Rituxan in 1606 patients, with exposures ranging from a single infusion up to 6–8 months. Rituxan was studied in both single-agent and active-controlled trials (n = 356 and n = 1250). These data were obtained in adults with low-grade, follicular, or DLBCL NHL. Most patients received Rituxan as an infusion of 375 mg/m2 per infusion, given as a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 doses, or following chemotherapy for up to 16 doses. Infusion Reactions In the majority of patients with NHL, infusion reactions consisting of fever, chills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first Rituxan infusion. Infusion reactions typically occurred within 30 to 120 minutes of beginning the first infusion and resolved with slowing or interruption of the Rituxan infusion and with supportive care (diphenhydramine, acetaminophen, and intravenous saline). The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. [See Boxed Warning, Warnings and Precautions.] Infections Serious infections (NCI CTCAE Grade 3 or 4), including sepsis, occurred in less than 5% of patients with NHL in the single-arm studies. The overall incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal 1%). [See Warnings and Precautions.] In randomized, controlled studies where Rituxan was administered following chemotherapy for the treatment of follicular or low-grade NHL, the rate of infection was higher among patients who received Rituxan. In diffuse large B-cell lymphoma patients, viral infections occurred more frequently in those who received Rituxan. Cytopenias and hypogammaglobulinemia In patients with NHL receiving rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in 48% of patients. These included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia was 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116 days). A single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences of hemolytic anemia following Rituxan therapy occurred during the single-arm studies. In studies of monotherapy, Rituxan-induced B-cell depletion occurred in 70% to 80% of patients with NHL. Decreased IgM and IgG serum levels occurred in 14% of these patients. Single-Agent Rituxan Adverse reactions in Table 1 occurred in 356 patients with relapsed or refractory, lowgrade or follicular, CD20-positive, B-cell NHL treated in single-arm studies of Rituxan administered as a single agent. Most patients received Rituxan 375 mg/m2 weekly for 4 doses. Table 1 Incidence of Adverse Events in ≥5% of Patients with Relapsed or Refractory, LowGrade or Follicular NHL, Receiving Single-agent Rituxan (N = 356)a,b practical perspective Adapting to Economic Uncertainty: The Transition from a Traditional Physician Practice Model to a True Business Model in Oncology by Beau Donegan, MBA, CEO, Newport Pacific Medical Associates Although healthcare was once considered to be a recession-proof industry, the recent economic downturn has many physician practices nationwide scrambling to cut costs, streamline operations, and increase revenue. According to a report from the Medical Group Management Association (MGMA), after reaching a peak in 2007, the median practice revenue collected per full-time-equivalent physician declined by 7.8% in 2008.1 In addition to decreasing revenue, expenses are also consuming an ever-larger proportion of those revenues, with the annual median total operating cost for multispecialty practices reaching 63.3% of total revenue in 2008 – up from 58.8% just 10 years ago.1 Nowhere is the negative impact of a down economy on managed care more apparent than in the specialty of medical oncology, where costly therapies are financed by the practice in the current buy-and-bill model and then subjected to the payors administrative delays in getting reimbursed. This puts an inordinate amount of financial strain on practices. While the sizeable overhead associated with this initial investment in product inventory was manageable in the past, due in part to average wholesale price (AWP)-based reimbursement and timely payment to providers, it now represents a significant loss in cash flow that can adversely affect practice profitability and even survivability. In the face of these significant economic challenges, oncology practices are being forced to severely cut costs outside of those associated with drug products. In a member survey by the Association of Community Cancer Centers (ACCC), 86% of respondents reduced travel and education, 65% renegotiated vendor contracts, 61% delayed equipment purchases, and 59% delayed construction projects.2 In all, nearly six in 10 members made changes to their cancer program as a result of the current economic recession. Still, these interventions serve only as a Band-Aid® on a much larger problem, and they may not be adequate to overcome the current economic climate. Patients referred to hospitals for chemotherapy administration rose from 11% in 2007 to 18% in 2009, as practices that cannot afford to treat these patients refer them to alternate sites of service.2 In these uncertain times, oncology practices may have to change their very core of operations not only in order to survive but also to position themselves to thrive in this changing healthcare arena. managedcareoncology.com 21 A TRUE BUSINESS MODEL Although oncology practices have been able to operate outside of the standard business model since their inception, the recent financial crunch necessitates a new way of looking at things. Oncology practices that have played according to their own set of rules for years must now look toward the tried-andtrue business models that serve as the norm outside of the industry. Facing the prospect of a recession, outside business models look at their product or service, determine their position within their industry, and define or redefine their business strategy for the upcoming year. They evaluate overhead, expenses, and places to streamline services to gain additional revenue. They may conduct industry studies to determine survivability and profitability in the future. This standard approach has not typically been feasible for physician practices because of the mandates, requirements, and regulatory restrictions imposed by governing bodies. For example, physicians cannot readily increase revenue from product or services because third-party payors determine reimbursement rates. In order to develop a profitable, sustainable oncology practice business model, practice administrators must first be willing to step outside of the medical community and reach out to those familiar with basic business models. This represents an important step because most healthcare business professionals have typically been groomed in healthcare alone and are often challenged in understanding external business processes. Conversely, nonhealthcare business professionals may lack insight into the inherent complexities of a regulated industry. Nevertheless, these “outsiders” are more likely to possess the type of outside-the-box thinking and fresh and focal perspectives that will prove beneficial in making impactful changes to well-established practice processes. These professionals may include professors from academia, retirees from Fortune 500 companies, or anyone else who has adequate business acumen outside of healthcare. While standard business models do not fully translate to the intricacies of healthcare, these models can be adjusted and prove more nimble in tough economic times. This is achieved via collaboration between existing healthcare professionals and nonhealthcare consultants to make them applicable for implementation in oncology practices. So where do you start? ■ Know your daily costs to run the practice. Your fixed costs (rent, insurance, labor) and variable costs (drugs, repairs, capital purchases, supplies) are both important. Once you know your daily cost, you know your revenue targets to break even and targets for profitability. Most practices focus on relative value units (RVUs) to determine productivity; however, in this economic climate, the focus must be on the expense and revenue in microscopic fashion. 22 managedcareoncology Quarter 1 2010 ■ ■ Know your days of service outstanding (DSO). This is the calculation of the number of days from date of service until you are paid for the services rendered. Under most payor contracts, they agree to pay within 30 days on “clean claims” (Medicare within 14 days). Since payment for most of your goods and services purchased are due within 30 days, having the revenue to pay expenses is obviously the goal. Every day over 30 days means your practice is financing patient care through increased product cost due to interest, late payment penalties, and financing to maintain cash flow. In some instances, these additional expenses outstrip any revenue margins you may have realized. Know your drug inventory. Most practices are very good at keeping minimal inventory; however, having even some drug surplus can be costly. For example, if your daily utilization runs $50,000 on average, just two days on hand means you have $100,000 less cash flow. Just-intime ordering based on 24-hour use allows you to buy and bill instantly. This requires strict adherence to scheduling patients and treating only patients who are scheduled. At Newport Pacific Medical Associates, the impact of DSO beyond 30 days was characterized as costing $60,000 in cash flow for every day the payor is allowed to stall payment. Therefore, a DSO of 50 days results in floating the payor $1.2 million in cash flow – a significant figure of which practice managers must be aware. In addition to quantifying and assessing these key practice-specific economic characteristics, practices should not be afraid to ask patients for payment up front. This completely different business model is not insensitive to the patients but rather keeps them at arm’s length. A patient’s insurance should be viewed in the same manner that a nonhealthcare business views a customer’s credit. Just as a consumer would not be able to drive a new car off the lot with only his or her word, physicians should not render services without proof of an adequate means to pay for services. This unconventional practice of requiring that deductibles be paid up front may eventually become more commonplace during the current economic downturn, and patients at Newport Pacific Medical Associates have been relatively receptive to the change. The practice sent a letter to patients in early December 2009 explaining that they could no longer finance patients at this time due to the increasing cost of therapy and increasingly higher copayments. While this is unheard of in the industry, once patients realized the cost of their therapies and what it costs the practice to finance them, most are complying with paying the deductible up front in 2010. It is important to note that the practice is not denying patients the ability to see their physician, but rather only refusing therapies for which payment can be collateralized or collected in advance. In addition to asking patients to partner with the practice in securing payment for services rendered, Newport Pacific Medical Associates likewise has asked patients to contact their insurance companies when payment for services has not been received within 30 days, as these accounts are converted to patient responsibility. The practice sponsored an impartial, neutral educational forum for patients only, thereby empowering patients to get to know their insurance. Since payors are more receptive to the concerns of their customers (i.e., the patients), patient requests are often more fruitful than exclusively practicedriven discussions. CONCLUSIONS The process of implementing an efficient business model at an oncology practice is not without its challenges. The current healthcare system is such that a substantive change in the way practices operate presents a difficult and convoluted process. Since many healthcare professionals have been “born and raised” in the business of healthcare, they are often not optimally equipped for managing practice operations in difficult economic times. This is not to say that nonhealthcare professionals are better or more knowledgeable than healthcare professionals in running a business, but rather that they lend a fresh perspective to the current, clinically astute medical staff of an oncology practice. Healthcare has been a sacred domain for years; however, in the U.S., healthcare is also a business. Whereas business has historically been a distasteful term, it is precisely that type of thinking that puts practices in peril in the midst of challenging financial times such as these. Implementing a business strategy in oncology does not mean that a practice should become less sensitive and compassionate toward its patients. Rather, it means that the practice is willing to minimize costs and be dynamic enough to change the way it does things. In light of recent developments, the healthcare industry finds itself on the precipice of change for the next three to five years. Unless practice managers are willing to undergo a strategic shift and adopt sound business models, the provision of oncology care will fail. These models need to be nimble and transparent so that practice managers can reassess, shift direction, and refocus when a particular model is not working. In the current economic climate, the bottom line is that practices will not be able to keep themselves afloat by doing the same things they have always done to maintain viability. References 1. Medical Group Management Association. Cost Survey for Multispecialty Practices: 2009. Englewood, CO: Medical Group Management Association; 2009. 2. Association of Community Cancer Centers. 2009 Cancer Care Trends in Community Cancer Centers Survey. Rockville, MD: Association of Community Cancer Centers; 2010. managedcareoncology.com 23 therapy reviews Pro 24 managedcareoncology Quarter 1 2010 ostate Cancer IN 2010 by Charles J. Ryan, MD, Assistant Clinical Professor, University of California, San Francisco School of Medicine Prostate cancer is the most common noncutaneous cancer in men in the U.S., and it is the sixth most common cancer in the world. The current lifetime risk for prostate cancer in men living in the U.S. is estimated at one in six. It is estimated that 192,280 men were diagnosed in 2009 and that 27,360 deaths will have occurred. Although early-stage disease is highly curable, approximately 50,000 to 60,000 men experience a relapse of the disease annually, and approximately 5% to 10% have metastatic disease at the time of diagnosis and are thus considered unable to be cured with surgery or radiation. Approximately 30,000 American men die of the disease every year. Death rates from prostate cancer have been steadily declining since the 1990s, a result of the combination of early detection and improved treatment of localized disease, as well as improved therapies for men with advanced disease. Advancing age is a major risk factor for the development of prostate cancer. While only one in 10,000 men younger than age 40 will develop prostate cancer, the odds increase to one in 103 for those between the ages of 40 and 59 and one in eight for those between the ages of 60 and 79. Certain population groups are at higher risk, including African-Americans and those with a family history of the disease. Men with a first-degree relative (brother, father, uncle) with prostate cancer have a higher likelihood of developing the disease; however, mortality from the disease is not different from those with the sporadic form. The epidemiology of the disease was altered substantially in the early 1990s with the onset of PSA (prostate-specific antigen) blood screening, which led to a significant increase in the incidence of the disease. Recently, two large randomized studies examined the rate of death from prostate cancer in patients who were screened versus a control population that was not screened. In the study conducted in the U.S., screening did not lead to a benefit in overall survival; while in a larger European study with longer follow-up, a lower rate of death from prostate cancer was noted. Of note, approximately 50% of the patients in the U.S. study who were placed in the no-screening group did undergo PSA testing, thus potentially contaminating the results. managedcareoncology.com 25 Figure 1. Location of the Prostate Prostate Seminal Vesicle Benign Enlargement Urethra Prostate Penis Cancerous Tumor Rectum Scrotum The management of prostate cancer is accomplished through a multidisciplinary approach that utilizes the expertise of urologists and medical and radiation oncologists. PATHOLOGY The prostate gland is approximately the size of a walnut and is located at the base of the bladder (see Figure 1). The primary role of the prostate gland in male physiology is the secretion of the fluid components of semen. Thus, the most common type of cancer arising from the prostate comes from the glandular tissue – a type of cancer known as an adenocarcinoma. More than 95% of prostate cancers are adenocarcinomas. Unlike adenocarcinomas that develop in other parts of the body (e.g., lung and colon), adenocarcinomas that arise in the prostate grow through the stimulation of androgen (e.g., testosterone) and express in high concentrations the androgen receptor (AR), which is activated by testosterone. The remainder of prostate cancers are neuroendocrine (i.e., small cell) cancers and transitional cell carcinomas (arising from the special lining cells of the urinary tract – similar to bladder cancer). Sarcomas can also arise in the prostate gland but are exceedingly rare. NATURAL HISTORY The vast majority of diagnosed prostate cancers are confined within the prostate gland and are thus termed “localized” disease – a situation in which curative treatment is possible. The fatal form of the disease arises from the situation in which the cancer has spread through the blood or lymph system to the bones (most commonly) or to other organs, such as the liver and lung (less common). Many patients who are diagnosed and treated for localized disease may harbor occult metastatic (distantly spread) disease in one or more of these other organs, which accounts for the 50,000 or so relapses that occur in the U.S. every year and the vast majority of the 30,000 annual deaths. Figure 2 shows the varied clinical “states” that are seen in the progression of prostate cancer. The most common site of distant spread (metastasis) is bone, particularly the lumbar spine, femur, and pelvis. CAUSES AND RISK FACTORS FOR PROSTATE CANCER It is likely that there is more than one underlying cause of prostate cancer, as there appear to be both genetic and environmental factors that contribute to its development. The role of genetics is an area of active investigation that will likely lead to significant advances in our ability to predict who will develop clinically significant prostate cancer. Such advances may lead to more accurate and detailed screening methods as well as molecular targeted therapies. Further, blocking the interaction of testosterone and its derivatives with the AR form the basis for the most effec- Figure 2. Clinical States of Prostate Cancer The following diagram demonstrates schematically the distinct form the disease takes through its long natural history, which varies based on the presence or absence of metastases as well as the use of androgen-deprivation therapy. 26 managedcareoncology Quarter 1 2010 Metastatic Disease (noncastrate) Localized Disease CastrationResistant Prostate Cancer Rising PSA (noncastrate) Rising PSA (castrate, no metastases) Adapted from Scher and Heller, Urology, 2000. quoted as such (e.g., “Gleason 3 + 3 = 6”) rather than the sum alone being stated. The reason for this is that the primary Gleason has a very strong prognostic value, and therefore, a Gleason 3 + 3 would be considered less aggressive than a Gleason 4 + 2. Gleason patterns 1 and 2 are very rarely found. tive means of controlling the growth of advanced disease. Many of the new medical therapies that have been developed or are in development for prostate cancer are derivations of this original approach. DIAGNOSTIC TESTING Symptoms – Most patients with early-stage prostate cancer do not have any symptoms of the disease and are diagnosed on the basis of screening. Urinary symptoms can occur that can be confused with the symptoms of benign prostatic hypertrophy (BPH). Bone pain, loss of appetite, weight loss, and fatigue are symptoms that can accompany metastatic disease. In rare but severe cases, nerve damage can occur, causing altered levels of sensation in the arms and legs, weakness in the legs, or a change in the level of bowel or bladder control. Biopsy – A prostate biopsy is considered when there is reasonable clinical suspicion based on digital rectal exam (DRE) and PSA results that prostate cancer exists. The procedure involves the insertion of a transrectal ultrasound (TRUS) probe into the patient’s rectum, allowing visualization of the gland. Subsequently, 8 to 16 “cores” are obtained with a 15-mm-long core biopsy needle. It is recommended that, at a minimum, a 12-mm core biopsy be used. Biopsy results may show cancer or other conditions that are not cancer per se but will require surveillance; these include atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HG PIN). Either one of these conditions merits close follow-up and repeat biopsies, as they may suggest a high risk for the development of cancer. STAGING/GRADING The most common grading system is the Gleason grading system in which two scores are derived and then “summed.” The tumors are assigned a number 1 to 5, where 1 represents the least aggressive appearing pattern and 5 represents the most aggressive appearing pattern. The Gleason score (or sum) is the combination of the primary and secondary Gleason grade and is often TREATMENT STRATEGIES Localized Prostate Cancer – Many treatment options are available for patients with localized early-stage prostate cancer. ■ Watchful waiting or active surveillance. The risk of disease progression is low in patients with Gleason scores 2 to 6 (with no pattern 4 or 5 present), T1 or T2a disease, and a serum PSA that is low and stable. Men with these features can be followed carefully and treated at the first sign of progression. Critical to the success of this approach is diligent surveillance and repeat biopsies (approximately yearly). Thus, active surveillance offers an opportunity to avoid or delay the side effects of radical treatment. The standards of care for surveillance (e.g., when to treat and how frequently to repeat biopsies) are in the process of development. A study conducted in Sweden in which patients were randomly selected to have surgery or active surveillance found that by 10 years there was a significant difference in the death rate from prostate cancer and an improvement overall in younger men (< 65 years old). Despite this, it is still possible that men with lowrisk disease who are diligent in their follow-up can undergo active surveillance and deferred therapy. ■ Radical prostatectomy. Radical prostatectomy involves the surgical removal of the prostate and seminal vesicles. Newer laparoscopic and managedcareoncology.com 27 ■ robotic approaches offer the option of treatment with smaller incisions and shorter hospitalization. The surgeon may elect to remove the pelvic lymph nodes in higher risk cases or if there is an intra-operative finding suggesting more advanced disease. Following prostatectomy, a urinary catheter is held in place for several days and patients are back to full activity within 2.5 to three weeks. Radiation therapy – external beam therapy. Several approaches in the management of localized prostate cancer involve the delivery of radiation to the cancerous tissue. The range of radiation approaches includes standard external beam radiation therapy (the radiation comes from a machine and is aimed at the prostate while the patient lies on a table) to the more modern techniques of three-dimensional conformal radiation therapy (3DCRT) and intensity modulated radiation therapy (IMRT), which allow radiation treatment to be given at higher doses in the prostate and lower doses elsewhere. Brachytherapy is a form of radiation in which “seeds” containing the radiation are permanently placed in the prostate gland. Permanent implants in the form of iodine-125 or palladium-103 radioactive seeds may be used. Other radiation techniques, such as highdose-rate (HDR) brachytherapy, a form of temporary radioactive seed implantation, are typically utilized in patients with higher risk disease in combination with external beam radiation and/or androgen deprivation. The outcome following radiation therapy can be enhanced for many with the addition of androgendeprivation therapy (ADT) before and during radiation treatment. In particular, ADT has been shown to improve the overall survival following radiation in patients with intermediate- and high-risk disease. Other Approaches to Localized Prostate Cancer (Hormonal Therapy) – Hormonal therapy in prostate cancer refers to any therapy that seeks to block the stimulation of the tumor(s) by testosterone. Hormonal therapy may be used at all stages of the disease and can induce prostate cancer cells into a prolonged state of hibernation and/or death. Medications known as LHRH (luteinizing hormone-releasing hormone) agonists are used to decrease testosterone production. This is frequently referred to as medical castration. LHRH agonists are given by injection and are available in preparations that exert their effect for periods ranging from one to 12 28 managedcareoncology Quarter 1 2010 months. An equally effective alternative to taking hormonal medications altogether is to stop the production of testosterone by having an orchiectomy (surgical removal of the testes). When the testosterone level has been lowered, the PSA tends to drop quickly and the prostate shrinks. There are additional androgens produced in the adrenal glands. In some situations, the addition of oral medications called anti-androgens that prevent androgens from entering the prostate cells may be beneficial. The combination of these two types of hormonal medications is known as total androgen blockage or complete androgen deprivation. These medications are occasionally used as primary treatment in many older patients with localized prostate cancer who do not undergo surgery or radiation. The duration of therapy with these medications varies. A commonly used strategy known as intermittent supportive and palliative therapies. The contemporary classification of the disease reflects the fact that it typically involves the progression through a series of distinct clinical “states” (see Figure 2), defined by the presence or absence of metastatic disease as well as detailing whether or not the disease is progressing in the context of a normal or low testosterone level (referred to as the “castrate state”). androgen deprivation is used to minimize the side effects of ADT. Androgen deprivation poses a substantial risk of side effects. The absence of testosterone (caused by LHRH agonists or orchiectomy) can produce a loss in the desire for sex, weight gain, hot flashes, loss of muscle strength, fatigue, osteoporosis, and occasionally depressive symptoms. An important recent observation is that ADT may increase the risk for diabetes, stroke, and heart attack. CLINICAL STATES OF PROSTATE CANCER For most patients who develop recurrent prostate cancer after undergoing local therapy with radiation or surgery, prostate cancer is managed as a chronic medical condition with combinations of androgen-deprivation therapy, secondary hormonal therapy, and chemotherapy in addition to various RISING PSA Approximately 50,000 to 60,000 American men develop a rising PSA after having already received local therapy with “curative intent.” Not all men who experience a relapse of the disease in the form of a rising PSA will go on to develop metastatic prostate cancer and many postsurgery patients may be cured with radiation therapy (if they have previously undergone radical prostatectomy). The rate of change in PSA over time (usually expressed as the PSA doubling time, or PSADT) is the single most accurate predictor of both metastases and death in the rising PSA clinical state. One study demonstrated that one-half of the patients with a PSADT < 3 developed metastatic tumors in the bone within 2.25 years, whereas it took approximately four years in those with a PSADT of three to six months (P < 0.001). Many patients with a rising PSA will ultimately require hormonal therapy in one form or another and a substantial number will go on to hormonal therapy before they develop metastases. TREATMENT OF METASTATIC DISEASE The standard initial treatment for patients with metastatic prostate cancer is ADT. There is some evidence to suggest that patients with metastatic disease who are treated with total androgen blockade demonstrate increased survival compared with patients treated with medical castration (LHRH agonist only). In most treated patients, certain populations of tumor cells adapt to and grow despite low levels of testosterone. This is known as castration-resistant prostate cancer (CRPC) or hormone-refractory prostate cancer (HRPC). A variety of secondary hormonal therapies are available and typically aim to further interrupt the ability of testosterone and its related hormones to stimulate the androgen receptor. A widely utilized drug is ketoconazole, which lowers the levels of testosteronelike hormones made by the adrenal glands. Other anti-androgens, such as nilutamide or flutamide, may be useful if a patient has received bicalutamide. Steroid drugs, like prednisone and dexamethasone, are also used, as are estrogens, such as diethylstilbestrol or estradiol. New drugs, such as abiraterone acetate, are showing promise in this area. Abiraterone is an inhibitor of CYP17, a critical enzyme in the production of adrenal androgens, and has shown response rates in the 50% to 85% range. MDV3100, a novel oral androgen receptor antagonist that was developed in a tumor model characterized by androgen receptor amplification, has been associated with significant responses in approximately 50% to 65% of patients, including many with prior chemotherapy exposure. This agent is currently being evaluated in a phase 3 study. For many patients with advanced prostate cancer, pain and bone complications (e.g., fractures) become a substantial risk. For such patients, an approach that combines bone protection with chemotherapy is frequently utilized. One drug, zoledronic acid, has been shown to managedcareoncology.com 29 reduce the rate of complications in the bone and is in widespread use in this setting. It is administered intravenously approximately once per month. A novel agent that targets RANK-ligandinduced bone loss, denosumab, is in late-stage development as a treatment for both bone loss and to prevent bone complications. CHEMOTHERAPY FOR CRPC Until recently, chemotherapy has been utilized with relatively little frequency in prostate cancer. This has had less to do with the effectiveness of chemotherapy against prostate cancer (many patients benefit significantly from chemotherapy) and more to do with the fact that definitive data from clinical trials of chemotherapy in this disease were lacking until the early part of this decade. It wasn’t until 2004 that an approach that utilized chemotherapy was shown to improve the survival of prostate cancer patients. Two simultaneously conducted phase 3 studies were presented in 2004 that compared docetaxel chemotherapy to mitoxantrone, a drug that had been approved for use in prostate cancer for its potential to palliate pain and improve quality of life, but not to improve survival. The most important of the two studies was the multinational “Tax 327” study, which utilized three treatment arms: docetaxel (35 mg/m2) administered intravenously once per week, vs. docetaxel (75 mg/ m2) given intravenously every three weeks, vs. mitoxantrone (12 mg/m2) administered every three weeks. In Tax 327, 90% of the patients had metastatic disease in the bone and approximately one-half had disease-related pain requiring opioid pain medications (e.g., morphine). The results of the Tax 327 study demonstrated that the median survival of all docetaxel-treated patients was 18.2 months, compared with 16.4 months for those treated with mitoxantrone, a difference that was statistically significant. An analysis of the survival in the docetaxel every-three-weeks arm was 18.9 months, which was significant when compared with the 16.4-month survival in those treated with M/P, and translated into a hazard ratio of 0.76 and a P value of 0.009 – in layperson’s terms, this means that patients who received docetaxel first lived 24% longer. The docetaxel given every 21 days was also superior to mitoxantrone with respect to pain response rate (35% vs. 22%; P = 0.01) and PSA response rate (45% vs. 32%; P = 0.0005). Based on the improvement in survival observed in patients receiving the docetaxel/ prednisone every 21 days in Tax 327, the U.S. Food and Drug Administration approved the use of docetaxel (75 mg/m2 every 21 days) together with prednisone as frontline therapy for metastatic HRPC in May 2004. Several new approaches to improving the efficacy of chemotherapy-based treatment are in development. Results are anticipated from an ongoing Table 1. Prostate Cancer Staging (Adapted from the American Joint Committee Cancer Staging Manual, 6th Edition) T1 tumors are those tumors that are not clinically palpable on DRE or visible on TRUS T1a – incidental finding of cancer in ≤ 5% of the tissue resected during a transurethral resection of the prostate T1b – incidental finding of cancer in ≥ 5% of the tissue resected during a transurethral resection of the prostate T1c – tumor identified by needle biopsy (performed because of an elevated PSA) T2 tumors are confined to the prostate, identified by DRE or TRUS T2a – tumor involves one-half of one lobe or less T2b – tumor involves more than one-half of one lobe but not both lobes T2c – tumor involves both lobes T3 tumors extend through the prostatic capsule T3a – extracapsular extension (unilateral or bilateral) T3b – tumor invades seminal vesicle(s) T4 tumors are fixed or invade adjacent structures, such as bladder neck, external sphincter, rectum, levator muscles, or pelvic wall N1 refers to regional lymph node metastasis M1 refers to distant metastasis M1a – nonregional lymph nodes M1b – bone(s) M1c – other site(s) 30 managedcareoncology Quarter 1 2010 phase 3 randomized double-blind study comparing standard docetaxel therapy to docetaxel/prednisone plus bevacizumab. The addition of bevacizumab to chemotherapy in other cancers has led to improvements in survival and responses to chemotherapy. The addition of calcitriol and vaccines has thus far not shown to be beneficial when added to docetaxel. In addition, early clinical studies suggest that ixabepilone has significant activity in men with HRPC both in chemotherapynaive and previously treated patients. Lastly, cabazitaxel (XRP-6258) is a taxane antineoplastic agent that works through the disruption of the microtubule network that is essential for mitotic and interphase cellular functions. By disruption of this network, inhibition of cell division and subsequent cell death occur. Cabazitaxel has shown a promising safety profile and activity in patients progressing after docetaxel therapy. Therefore, cabazitaxel is currently being investigated in the management of prostate cancer that has been previously treated with docetaxel. Therapies that seek to augment the body’s immune reaction against prostate cancer are also in late-stage clinical trials. In therapy based on the sipuleucel-T vaccine, dendritic cells (the cells that initiate an immune response) are removed from the body and incubated with a prostate cancer antigen (prostatic acid phosphatase) and reinfused into the body three times. Prior studies have suggested that patients who received this vaccine had a longer survival than patients who received a placebo, and the confirmatory studies are under way. Should this approach prove useful in late-stage disease, it is possible that these vaccines may be used to prevent or delay recurrence in patients who have been treated with radiation or surgery with curative intent. CONCLUSION Prostate cancer is a very common disease with an extremely varied natural history. The optimal management of patients with prostate cancer is highly individualized, based on the varied aggressiveness of the disease ranging from one that is capable of being observed without therapy to one that is lethal for many patients (see Table 1). The optimal treatment program for an individual patient is one in which a multidisciplinary team of clinicians is involved in clinical decision making and treatment planning. Further, the aging of the population raises the possibility that more men than ever will deal with advanced prostate cancer, highlighting the urgency for the development of new therapies. Investigation of new therapies in the form of clinical trial enrollment is a critical factor in proving their success or failure and should be encouraged whenever possible. References 1. Andriole GL, Crawford ED, Grubb RL, et al. Mortality results from a randomized prostate cancer screening trial. N Engl J Med. 2009;360(13):1310-1319. 2. Mehta S, Lubeck D, Sadetsky N. Patterns of secondary cancer treatment for biochemical failure following radical prostatectomy: data from CaPSURE. J Urol. 2004;171:215-219. 3. Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513-1520. 4. Ryan CJ, Eisenberger M. Chemotherapy for hormone-refractory prostate cancer: now it’s a question of “when?” J Clin Oncol. 2005;23(32):8242-8246. 5. Ryan CJ, Small EJ. Early versus delayed androgen deprivation for prostate cancer: new fuel for an old debate. J Clin Oncol. 2005;23(32):8225-8231. 6. Scher HI, Heller G. Clinical states in prostate cancer: towards a dynamic model of disease progression. Urol. 2000;55:323-327. 7. Schröder FH, van den Bergh RC, Wolters T, et al. Eleven-year outcome of patients with prostate cancers diagnosed during screening after initial negative sextant biopsies. Eur Urol. 2010;57(2):256-266. 8. Smith MR, Kabbinavar F, Saad F, et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23(13):2918-2925. 9. Stephenson AJ, Shariat SF, Zelefsky MJ, et al. Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. JAMA. 2004;291(11):1325-1332. 10. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502-1512. 11. Zelefsky MJ, Ben-Parat L, Scher HI, et al. Outcome predictors for the increasing PSA state after definitive external-beam radiotherapy for prostate cancer. J Clin Oncol. 2005;23(4):826-831. managedcareoncology.com 31 Drug & Administration compendia Treatment of Prostate Cancer With each publication, Managed Care Oncology’s Drug & Administration Compendia highlights a single medication or a group of medications that could be utilized in the management of one of the featured oncology diseases. This section addresses such topics as: • AssociatedICD-9-CMcodesthatcanbeutilizedforthefeaturedoncologydisease • DrugsthathavebeenFDA-approvedorarelistedintheNCCN™(NationalComprehensive Cancer Network) Drugs & Biologics Compendium for off-label use Please note: The NCCN is recognized by CMS (Centers for Medicare & Medicaid Services) as a referencing source. • Ancillarymedicationsusedincancertreatment • Reimbursementandcodinginformation o HCPCS/CPT codes and code description o Current code price (AWP-based pricing) o Most recent Medicare allowable (ASP + 6%) o Possible CPT administration codes that can be utilized with each drug Associated ICD-9-CM Codes: 185 Malignant neoplasm of prostate Excludes seminal vesicles (187.8) 32 managedcareoncology Quarter 1 2010 FDA-Approved Medications Currently Available to Treat Prostate Cancer generic (Brand) Name HCPCS Code – Code Description Current Code Price (AWP-Based Pricing) Effective 2/1/10 Medicare Allowable (ASP + 6%) Effective 1/1/10-3/31/10 CPT Administration Code(s) bicalutamide (Casodex) J8999 – prescription drug, oral, chemotherapeutic, not otherwise specified NDC level pricing NDC level pricing N/A degarelix (Firmagon) J9155 – injection, degarelix, 1 mg (for billing prior to 1/1/10, use J9999 or C9399) $4.67 $2.87 96402 docetaxel (Taxotere) J9171 – injection, docetaxel, 1 mg $23.23 $17.62 96413 estramustine (Emcyt) J8999 – prescription drug, oral, chemotherapeutic, not otherwise specified NDC level pricing NDC level pricing N/A flutamide (Eulexin) J8999 – prescription drug, oral, chemotherapeutic, not otherwise specified NDC level pricing NDC level pricing N/A goserelin acetate (Zoladex) J9202 – goserelin acetate implant, per 3.6 mg $451.19 $203.87 96372, 96402 histrelin (Vantas) J9225 – histrelin implant (Vantas), 50 mg $6,000.00 $1,462.69 11981, 11982, 11983 leuprolide acetate (Eligard, Lupron Depot) J9217 – leuprolide acetate (for depot suspension), 7.5 mg $493.20 $206.52 96402 leuprolide acetate (Lupron) J9218 – leuprolide acetate, per 1 mg $27.52 $4.77 96402 mitoxantrone (Novantrone) J9293 – injection, mitoxantrone hydrochloride, per 5 mg $116.50 $47.77 96409, 96413 nilutamide (Nilandron) J8999 – prescription drug, oral, chemotherapeutic, not otherwise specified NDC level pricing NDC level pricing N/A triptorelin (Trelstar Depot, Trelstar LA) J3315 – injection, triptorelin pamoate, 3.75 mg $870.00 $156.38 96372, 96402 NCCN Compendia-Listed Medications Currently Available to Treat Prostate Cancer generic (Brand) Name HCPCS Code – Code Description Current Code Price (AWP-Based Pricing) Effective 2/1/10 Medicare Allowable (ASP + 6%) Effective 1/1/10-3/31/10 CPT Administration Code(s) bacillus Calmette-Guérin (Tice BCG) 90585 – bacillus Calmette-Guérin vaccine (BCG) for tuberculosis, live, for percutaneous use $169.10 $110.22 90471 carboplatin (Paraplatin) J9045 – injection, carboplatin, 50 mg $48.55 $4.84 96409, 96413, 96415 cisplatin (Platinol AQ) J9060 – cisplatin, powder or solution, per 10 mg $4.33 $2.08 96409, 96413, 96415 cisplatin (Platinol AQ) J9062 – cisplatin, 50 mg $21.66 $10.41 96409, 96413, 96415 doxorubicin (Adriamycin) J9000 – injection, doxorubicin hydrochloride, 10 mg $13.20 $3.48 96409 etoposide preservative-free (Etopophos) J9181 – injection, etoposide, 10 mg $0.53 $0.45 96413, 96415 etoposide (Vepesid) J8999 – prescription drug, oral, chemotherapeutic, not otherwise specified NDC level pricing NDC level pricing N/A gemcitabine (Gemzar) J9201 – injection, gemcitabine hydrochloride, 200 mg $173.83 $144.93 96413 managedcareoncology.com 33 NCCN Compendia-Listed Medications Currently Available to Treat Prostate Cancer generic (Brand) Name HCPCS Code – Code Description Current Code Price (AWP-Based Pricing) Effective 2/1/10 Medicare Allowable (ASP + 6%) Effective 1/1/10 – 3/31/10 CPT Administration Code(s) ketoconazole (Nizoral) J8499 – prescription drug, oral, nonchemotherapeutic, not otherwise specified NDC level pricing NDC level pricing N/A methotrexate J9250 – methotrexate sodium, 5 mg $0.29 $0.25 96372, 96374, 96401, 96409, 96450 methotrexate J9260 – methotrexate sodium, 50 mg $2.86 $2.46 96372, 96374, 96401, 96409, 96450 paclitaxel (Taxol) J9265 – injection, paclitaxel, 30 mg $17.70 $9.43 96413, 96415 prednisone (Deltasone) J7506 – prednisone, oral, per 5 mg $0.05 $0.05 N/A vinblastine J9360 – injection, vinblastine sulfate, 1 mg $3.18 $1.11 96409 Ancillary Medications Used in Cancer Treatment generic (Brand) Name HCPCS Code – Code Description Current Code Price (AWP-Based Pricing) Effective 2/1/10 Medicare Allowable (ASP + 6%) – Effective 1/1/10-3/31/10 CPT Administration Code(s) aprepitant (Emend) J8501 – aprepitant, oral, 5 mg $6.85 $5.53 N/A granisetron (Kytril) J1626 – injection, granisetron hydrochloride, 100 mcg $10.61 $1.27 96374 granisetron (Kytril) Q0166 – granisetron hydrochloride, 1 mg oral, FDAapproved prescription anti-emetic, for use as a complete therapeutic substitute for an IV anti-emetic at time of chemotherapy treatment, not to exceed a 24-hour dosage regimen $59.01 $7.31 N/A granisetron (Kytril) S0091 – granisetron hydrochloride, 1 mg (for circumstances falling under the Medicare statute, use Q0166) $59.01 S0091– not payable by Medicare N/A ondansetron (Zofran) J2405 – injection, ondansetron hydrochloride, per 1 mg $0.60 $0.24 96372, 96374 ondansetron (Zofran) Q0179 – ondansetron hydrochloride, 8 mg, oral, FDAapproved prescription anti-emetic, for use as a complete therapeutic substitute for an IV anti-emetic at time of chemotherapy treatment, not to exceed a 48-hour dosage regimen (code price is per 8 mg) $39.36 $6.81 N/A ondansetron (Zofran) S0181 – ondansetron HCl, oral, 4 mg (for circumstances falling under the Medicare statute, use Q0179) $23.98 S0181– not payable by Medicare N/A palonosetron (Aloxi) J2469 – injection, palonosetron HCl, 25 mcg $41.88 $17.51 96374 34 managedcareoncology Quarter 1 2010 CPT Administration Code Descriptions CPT Administration Code Code Description 96401 Chemotherapy administration, subcutaneous or intramuscular; nonhormonal antineoplastic 96402 Chemotherapy administration, subcutaneous or intramuscular; hormonal antineoplastic 96409 Chemotherapy administration; intravenous, push technique, single or initial substance/drug 96411 Chemotherapy administration; intravenous, push technique, each additional substance/drug (List separately in addition to code for primary procedure.) (Use 96411 in conjunction with 96409 and 96413.) 96413 Chemotherapy administration, intravenous infusion technique; up to one hour, single or initial substance/drug 96415 Chemotherapy administration, intravenous infusion technique; each additional hour (List separately in addition to code for primary procedure.) (Use 96415 in conjunction with 96413.) 96416 Chemotherapy administration, intravenous infusion technique; initiation of prolonged chemotherapy infusion (more than eight hours), requiring use of a portable or implantable pump 96417 Chemotherapy administration, intravenous infusion technique; each additional sequential infusion (different substance/drug), up to one hour (List separately in addition to code for primary procedure.) (Use 96417 in conjunction with 96413.) 96422 Chemotherapy administration, intra-arterial; infusion technique, up to one hour 96423 Chemotherapy administration, intra-arterial; infusion technique, each additional hour (List separately in addition to code for primary procedure.) (Use 96423 in conjunction with 96422.) 96425 Chemotherapy administration, intra-arterial; infusion technique, initiation of prolonged infusion (more than eight hours), requiring the use of a portable or implantable pump 96450 Chemotherapy administration, into CNS (e.g., intrathecal), requiring and including spinal puncture 96365 Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to one hour 96366 Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); each additional hour (List separately in addition to code for primary procedure.) (Use 96366 in conjunction with 96365, 96367.) 96369 Subcutaneous infusion for therapy or prophylaxis (specify substance or drug); initial, up to one hour, including pump setup and establishment of subcutaneous infusion site(s) 96370 Subcutaneous infusion for therapy or prophylaxis (specify substance or drug); each additional hour (List separately in addition to code for primary procedure.) (Use 96370 in conjunction with 96369.) 96372 Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular 96374 Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); intravenous push, single, or initial substance/drug 11981 Insertion, nonbiodegradable drug delivery implant 11982 Removal, nonbiodegradable drug delivery implant 11983 Removal with reinsertion, nonbiodegradable drug delivery implant Prostate Cancer References •HCPCSLevelIIExpert2010. •CurrentProceduralTerminology(CPT)2010. •AmericanMedicalAssociation.Professional ICD-9-CM for Physicians, Volumes 1 and 2. AMA Press. 2010. •RJHealthSystemsInternational,LLC.The Drug Reimbursement Coding and Pricing Guide. Volume 7, Number 1, First Quarter 2010. •FDA-approvedindication(product-prescribinginformation). •TheNCCNDrugs&BiologicsCompendium™©2010NationalComprehensiveCancerNetwork,Inc.Availableatwww.nccn.org.AccessedJanuary1,2010.Toviewthemostrecentandcompleteversion of the NCCN Compendium, go online to www.nccn.org. •www.ReimbursementCodes.com.PoweredbyRJHealthSystemsInternationalLLC,Wethersfield,Conn. •CMS(CentersforMedicare&MedicaidServices)–Medicare-AllowableFirstQuarter2010–EffectiveDates:1/1/10-3/31/10. This information was supplied by RJ Health Systems International, LLC, located in Wethersfield, Conn. Prices and information supplied herein are effective as of February 1, 2010. managedcareoncology.com 35 Oncology-Related HCPCS Codes This reference chart will assist the Oncology Office (office manager, oncology nurse, physician, and ancillary staff) and payor with the appropriate codes to utilize when billing or reimbursing for medication(s). Current Code Price (AWP- Based Pricing)* Medicare Allowable (ASP + 6%)** CPT Admin Code(s) generic (Brand) Name HCPCS Code – Code Description azacitidine (Vidaza) J9025 – injection, azacitidine, 1 mg Myeloid leukemia – chronic (205.1_) Low-grade myelodysplastic syndrome lesions (238.72) High-grade myelodysplastic syndrome lesions (238.73) Myelodysplastic syndrome with 5q deletion (238.74) Myelodysplastic syndrome, unspecified (238.75) N/A $5.74 $4.89 96401 96409 96413 darbepoetin alfa (Aranesp) J0881 – injection, darbepoetin alfa, 1 mcg (non-ESRD use) J0882 – injection, darbepoetin alfa, 1 mcg (for ESRD on dialysis) Anemia in chronic kidney disease (285.21) Antineoplastic chemotherapy-induced anemia (285.3) Myeloid leukemia – chronic – without mention of having achieved remission (205.10) Low-grade myelodysplastic syndrome lesions (238.72) Myelodysplastic syndrome, unspecified (238.75) Iron-deficiency anemia, unspecified (280.9) Anemia in neoplastic disease (285.22) Anemia, unspecified (285.9) Encounter for antineoplastic chemotherapy (V58.11) Convalescence and palliative care – following chemotherapy (V66.2) $6.08 $2.83 96372 96374 daunorubicin (Cerubidine) J9150 – injection, daunorubicin, 10 mg Lymphoid leukemia – acute (204.0_) Myeloid leukemia – acute (205.0_) Monocytic leukemia – acute (206.0_) Acute erythremia and erythroleukemia (207.0_) Megakaryocytic leukemia (207.2_) Leukemia of unspecified cell type – acute (208.0_) Lymphosarcoma (200.1_) $25.20 $16.97 96409 96413 cetuximab (Erbitux) J9055 – injection, cetuximab, 10 mg Malignant neoplasm of colon (153._) Malignant neoplasm of rectum, rectosigmoid junction, and anus (154._) Malignant neoplasm of lip (140._) Malignant neoplasm of tongue (141._) Malignant neoplasm of major salivary glands (142._) Malignant neoplasm of gum (143._) Malignant neoplasm of floor of mouth (144._) Malignant neoplasm of other and unspecified parts of mouth (145._) Malignant neoplasm of oropharynx (146._) Malignant neoplasm of nasopharynx (147._) Malignant neoplasm of hypopharynx (148._) Malignant neoplasm of other and ill-defined sites within the lip, oral cavity, and pharynx (149._) Malignant neoplasm of nasal cavities, middle ear, and accessory sinuses (160._) Malignant neoplasm of larynx (161._) Malignant neoplasm of other and ill-defined sites – head, face, and neck (195.0) Secondary and unspecified malignant neoplasm of lymph nodes – lymph nodes of head, face, and neck (196.0) Malignant neoplasm of trachea, bronchus, and lung (162._) Other malignant neoplasm of skin – skin of lip (173.0) Secondary malignant neoplasm of respiratory and digestive systems – lung (197.0) Secondary malignant neoplasm of respiratory and digestive systems – liver, specified as secondary (197.7) Neoplasm of uncertain behavior of digestive and respiratory systems – lip, oral cavity, and pharynx (235.1) Neoplasm of uncertain behavior of digestive and respiratory systems – larynx (235.6) $57.60 $49.73 96413 96415 FDA-Approved Uses 36 managedcareoncology Quarter 1 2010 Compendia-ListedUses(NCCN™) Current Code Price (AWP- Based Pricing)* Medicare Allowable (ASP + 6%)** CPT Admin Code(s) generic (Brand) Name HCPCS Code – Code Description decitabine (Dacogen) J0894 – injection, decitabine, 1 mg Low-grade myelodysplastic syndrome lesions (238.72) High-grade myelodysplastic syndrome lesions (238.73) Myelodysplastic syndrome with 5q deletion (238.74) Myelodysplastic syndrome, unspecified (238.75) Myeloid leukemia – chronic – without mention of having achieved remission (205.10) Myeloid leukemia – chronic – in relapse (205.12) $34.13 $29.24 96413 96415 epoetin alfa (Procrit, Epogen) J0885 – injection, epoetin alfa (for non-ESRD use), 1,000 units J0886 – injection, epoetin alfa, 1,000 units (for ESRD on dialysis) (Renal dialysis facilities and hospitals must use code Q4081 effective 1/1/07.) Q4081 – injection, epoetin alfa, 100 units (for ESRD on dialysis) (for renal dialysis facilities and hospital use) Secondary to blood loss – chronic (280.0) Other specified aplastic anemias (284.89) Acute posthemorrhagic anemia (285.1) Anemia in chronic kidney disease (285.21) Antineoplastic chemotherapy-induced anemia (285.3) Primarily systemic agents – antineoplastic antibiotics (E930.7) Other anti-infectives – antiviral drugs (E931.7) Myeloid leukemia – chronic – without mention of having achieved remission (205.10) Low-grade myelodysplastic syndrome lesions (238.72) Myelodysplastic syndrome, unspecified (238.75) Iron-deficiency anemia, unspecified (280.9) Anemia in neoplastic disease (285.22) Anemia, unspecified (285.9) Encounter for antineoplastic chemotherapy (V58.11) Convalescence and palliative care – following chemotherapy (V66.2) J0885, J0886 $15.18 J0885, J0886 $9.54 96372 96374 Q4081 $1.52 Q4081 $0.95 filgrastim (Neupogen) J1440 – injection, filgrastim (G-CSF), 300 mcg Neutropenia, unspecified (288.00) Congenital neutropenia (288.01) Cyclic neutropenia (288.02) Drug-induced neutropenia (288.03) Neutropenia due to infection (288.04) Other neutropenia (288.09) Hemophagocytic syndromes (288.4) Leukocytopenia, unspecified (288.50) Other decreased white blood cell count (288.59) Primarily systemic agents – antineoplastic antibiotics (E930.7) Primarily systemic agents – antineoplastic and immunosuppressive drugs (E933.1) Myeloid leukemia – chronic – without mention of having achieved remission (205.10) Low-grade myelodysplastic syndrome lesions (238.72) Myelodysplastic syndrome, unspecified (238.75) Other prophylactic measure (V07.8) Encounter for antineoplastic chemotherapy (V58.11) Convalescence and palliative care – following chemotherapy (V66.2) $267.24 $219.71 96365 96366 96369 96370 96372 96374 filgrastim (Neupogen) J1441 – injection, filgrastim (G-CSF), 480 mcg Neutropenia, unspecified (288.00) Congenital neutropenia (288.01) Cyclic neutropenia (288.02) Drug-induced neutropenia (288.03) Neutropenia due to infection (288.04) Other neutropenia (288.09) Hemophagocytic syndromes (288.4) Leukocytopenia, unspecified (288.50) Other decreased white blood cell count (288.59) Primarily systemic agents – antineoplastic antibiotics (E930.7) Primarily systemic agents – antineoplastic and immunosuppressive drugs (E933.1) Myeloid leukemia – chronic – without mention of having achieved remission (205.10) Low-grade myelodysplastic syndrome lesions (238.72) High-grade myelodysplastic syndrome lesions (238.73) Myelodysplastic syndrome with 5q deletion (238.74) Myelodysplastic syndrome, unspecified (238.75) Other prophylactic measure (V07.8) Encounter for antineoplastic chemotherapy (V58.11) Convalescence and palliative care – following chemotherapy (V66.2) $425.58 $342.73 96365 96366 96369 96370 96372 96374 FDA-Approved Uses Compendia-ListedUses(NCCN™) managedcareoncology.com 37 Current Code Price (AWP- Based Pricing)* Medicare Allowable (ASP + 6%)** CPT Admin Code(s) generic (Brand) Name HCPCS Code – Code Description FDA-Approved Uses Compendia-ListedUses(NCCN™) floxuridine (FUDR) J9200 – injection, floxuridine, 500 mg Malignant neoplasm of stomach (151._) Malignant neoplasm of small intestine, including duodenum (152._) Malignant neoplasm of liver and intrahepatic bile ducts (155._) Secondary malignant neoplasm of respiratory and digestive systems – liver, specified as secondary (197.7) Malignant neoplasm of colon (153._) Malignant neoplasm of rectum, rectosigmoid junction, and anus (154._) Malignant neoplasm of kidney and other and unspecified urinary organs – kidney, except pelvis (189.0) Malignant neoplasm of kidney and other and unspecified urinary organs – renal pelvis (189.1) Urinary organs – kidney (V10.52) $121.06 $43.68 96422 96423 96425 idarubicin (Idamycin) J9211 – injection, idarubicin hydrochloride, 5 mg Myeloid leukemia – acute (205.0_) N/A $360.00 $102.83 96409 oxaliplatin (Eloxatin) J9263 – injection, oxaliplatin, 0.5 mg Malignant neoplasm of colon (153._) Malignant neoplasm of rectum, rectosigmoid junction, and anus (154._) Malignant neoplasm of esophagus (150._) Malignant neoplasm of stomach (151._) Malignant neoplasm of liver and intrahepatic bile ducts (155.1) Malignant neoplasm of gallbladder and extrahepatic bile ducts (156._) Malignant neoplasm of pancreas – head of pancreas (157.0) Malignant neoplasm of pancreas – body of pancreas (157.1) Malignant neoplasm of pancreas – tail of pancreas (157.2) Malignant neoplasm of pancreas – pancreatic duct (157.3) Malignant neoplasm of pancreas – other specified sites of pancreas (157.8) Malignant neoplasm of pancreas – pancreas, part unspecified (157.9) Malignant neoplasm of retroperitoneum and peritoneum – specified parts of peritoneum (158.8) Malignant neoplasm of ovary and other uterine adnexa (183._) Malignant neoplasm of testis (186._) Secondary malignant neoplasm of respiratory and digestive systems – lung (197.0) Secondary malignant neoplasm of respiratory and digestive systems – liver, specified as secondary (197.7) Marginal zone lymphoma (200.3_) Mantle cell lymphoma (200.4_) Anaplastic large-cell lymphoma (200.6_) Large-cell lymphoma (200.7_) Nodular lymphoma (202.0_) Peripheral T-cell lymphoma (202.7_) Other lymphomas (202.8_) Neoplasm of uncertain behavior of digestive and respiratory systems – other and unspecified digestive organs (235.5) Personal history of malignant neoplasm – gastrointestinal tract, unspecified (V10.00) Personal history of malignant neoplasm – esophagus (V10.03) Personal history of malignant neoplasm – testis (V10.47) $8.59 $7.62 96413 96415 38 managedcareoncology Quarter 1 2010 Current Code Price (AWP- Based Pricing)* Medicare Allowable (ASP + 6%)** CPT Admin Code(s) generic (Brand) Name HCPCS Code – Code Description paclitaxel proteinbound particles (Abraxane) J9264 – injection, paclitaxel protein-bound particles, 1 mg Malignant neoplasm of female breast (174._) Malignant neoplasm of male breast (175._) Malignant neoplasm of trachea, bronchus, and lung (162._) $11.20 $9.38 96413 panitumumab (Vectibix) J9303 – injection, panitumumab, 10 mg Malignant neoplasm of colon (153._) Malignant neoplasm of rectum, rectosigmoid junction, and anus (154._) Secondary malignant neoplasm of respiratory and digestive systems – lung (197.0) Secondary malignant neoplasm of respiratory and digestive systems – liver, specified as secondary (197.7) $101.85 $86.99 96413 96415 pegaspargase (Oncaspar) J9266 – injection, pegaspargase, per single-dose vial Lymphoid leukemia – acute (204.0_) N/A $3,280.00 $2,747.30 96401 96413 96415 pegfilgrastim (Neulasta) J2505 – injection, pegfilgrastim, 6 mg Neutropenia, unspecified (288.00) Drug-induced neutropenia (288.03) Neutropenia due to infection (288.04) Primarily systemic agents – antineoplastic antibiotics (E930.7) Primarily systemic agents – antineoplastic and immunosuppressive drugs (E933.1) Other prophylactic measure (V07.8) Encounter for antineoplastic chemotherapy (V58.11) Convalescence and palliative care – following chemotherapy (V66.2) $3,762.00 $2,364.70 96372 trastuzumab (Herceptin) J9355 – injection, trastuzumab, 10 mg Malignant neoplasm of female breast (174._) Malignant neoplasm of male breast (175._) Malignant neoplasm of esophagus (150._) Malignant neoplasm of stomach (151._) Neoplasm of uncertain behavior of digestive and respiratory systems – other and unspecified digestive organs (235.5) $76.35 $64.78 96413 96415 FDA-Approved Uses Compendia-ListedUses(NCCN™) * The code price is based on the Healthcare Common Procedure Coding System (HCPCS) code description. HCPCS codes are a component of CMS (Centers for Medicare & Medicaid Services). The code price is an AWP-based pricing methodology developed by RJ Health Systems International, LLC, Wethersfield, Conn. Effective as of 2/1/10. ** Effective 1/1/10-3/31/10 Oncology Related J-Code References: • HCPCSLevelIIExpert2010. • CurrentProceduralTerminology(CPT)2010. • TheNCCNDrugs&BiologicsCompendium™©2010NationalComprehensiveCancerNetwork,Inc.Availableatwww.nccn.org.AccessedJanuary1,2010.Toviewthemostrecentandcompleteversionofthe NCCN Compendium, go online to www.nccn.org. • AmericanMedicalAssociation.Professional ICD-9-CM 2009 Volumes 1 and 2. AMA Press, 2010. • Fullprescribinginformationforeachdruglisted. • RJHealthSystemInternational,LLC.The Drug Reimbursement Coding and Pricing Guide. Volume 7, Number 1, First Quarter 2010. • www.ReimbursementCodes.com.PoweredbyRJHealthSystemsInternationalLLC,Wethersfield,Conn. • CMS(CentersforMedicare&MedicaidServices)–Medicare-AllowableFirstQuarter–EffectiveDates:1/1/10-3/31/10 • Currentcodepricesareeffectiveasof2/1/10. managedcareoncology.com 39 clinical trial update by John W. Mucenski, BS, PharmD, Director of Pharmacy Operations, UPMC Cancer Centers New drug combinations such as docetaxel and gemcitabine do not appear to increase progressionfree or overall survival in patients with castraterefractory prostate cancer. Advances may be found in the appropriate use of drug combinations that incorporate drugs with unique mechanisms of action, such as dasatinib and abiraterone acetate. Further studies will define the utility of these agents. Title: Multinational, double-blind phase 3 study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. Authors: Sternberg CN, Petrylak DP, Sartor O, et al. Reference: J Clin Oncol. 2009;27:54315438. Purpose: Prostate cancer is the second most common malignancy of men worldwide. Docetaxel (Taxotere) was approved in 2004 as first-line therapy for castrate-refractory prostate cancer and is now considered the standard of care. However, all patients will discontinue the drug secondary to either disease progression or drugrelated toxicity. Presently, there is no second-line therapy that has significantly improved progressionfree survival (PFS) or overall survival (OS). Satraplatin is a novel, oral platinum compound that has preclinical activity in prostate cancer. A phase 2 trial demonstrated activity in castrate-refractory prostate cancer with myelosuppression being the dose-limiting toxicity. This phase 3 trial was initiated to determine the efficacy and tolerability of satraplatin in men with castrate-refractory prostate cancer who had progressed following one prior chemotherapy regimen. Methods: Patients with stage D2 (TxNxM1) metastatic adenocarcinoma of the prostate who had progressed following one prior chemotherapy regimen were eligible. Other inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2, surgical or medical castration (serum testosterone < 50 ng/dl), and adequate end-organ function. Patients were stratified based upon PS (0 or 1 vs. 2) and type of disease progression after prior therapy (tumor progression vs. prostate-specific antigen increase). Patients were randomized 2:1 to receive satraplatin 80 mg/m2 or 40 managedcareoncology Quarter 1 2010 placebo orally once daily on days one through five every 35 days. All patients received prednisone 5 mg orally twice a day on a continuous basis. Crossover between treatment arms was not permitted. The primary endpoints of the study were PFS and OS. Secondary endpoints included time to pain progression (TPP) as defined by an increased present pain intensity (PPI) score of ≥ 1 point from baseline or ≥ 2 points from nadir for ≥ two consecutive weeks, or a more than 25% increase from baseline in weekly average analgesic score for ≥ two consecutive weeks. Results: Nine hundred and fifty patients were enrolled, 635 receiving satraplatin and 315 receiving placebo. Patients were evenly matched in regards to age, ECOG PS, pain index, progression at study entry, and prior chemotherapy. Median PFS was 11.1 weeks (range 10.3 to 12.3 weeks) in the satraplatin arm and 9.7 weeks (range 9.3 to 10.0 weeks) in the placebo arm, which was statistically significant (p < 0.001). Median OS was 61.4 weeks for those patients treated with satraplatin and 61.4 weeks for those patients treated with placebo. This was not statistically significant. Median TPP favored satraplatin (66.1 weeks) vs. placebo (22.3 weeks) with a 36% reduction in the risk for pain progression with satraplatin therapy (p < 0.001). Tumor response, complete or partial, also favored satraplatin (8% vs. 0.7%; p = 0.002). As expected, hematologic toxicities were dose-limiting in those patients treated with satraplatin. Gastrointestinal disorders were also more common. Conclusion: Oral satraplatin delayed progression of disease in patients with metastatic castrate-refractory prostate cancer who experienced progression after initial chemotherapy, but it did not provide a significant OS benefit. The drug was well-tolerated. Managed Care Implications: Treatment for metastatic castrate-refractory prostate cancer in patients who have failed first-line chemotherapy continues to evolve. Oral agents such as satraplatin may offer an alternative for these patients. Presently the U.S. Food and Drug Administration (FDA) is awaiting additional data on the drug in this patient population before deciding whether to approve the drug for this indication. Title: Phase 2 study of dasatinib in patients with metastatic castrationresistant prostate cancer. Authors: Yu EY, Wilding G, Posadas E, et al. Reference: Clin Cancer Res. 2009;15(23):7421-8. Purpose: Prostate cancer that is not cured with local therapy results in metastases, primarily to bone, to which second-line hormonal therapies usually result in brief responses in less than half the patients treated. Docetaxel (Taxotere) chemotherapy has been shown to extend survival in men with metastatic castrationresistant prostate cancer (CRPC) but is associated with significant adverse events including myelosuppression, neuropathies, and fatigue. Dasatinib (Sprycel) is an oral tyrosine kinase inhibitor with activity against SRC family kinases (SFK), which are commonly overexpressed in prostate cancer lines. The drug is also known to have activity vs. BCR-ABL, plateletderived growth factor receptor, and c-KIT. SKFs also play a significant role in osteoclast and osteoblast function. Inhibition of SKFs has been shown to delay the appearance of bony metastases in murine models of breast cancer. Dasatinib has been shown in preclinical trials to inhibit the proliferation of prostate cancer cells, decrease prostate-specific antigen (PSA) levels, and increase bone mineral density. This phase 2 study was conducted to evaluate the efficacy and safety of dasatinib in patients with metastatic CRPC and increasing PSA levels. Methods: This open-label study was conducted at 10 centers in the U.S. and Europe. Patients had to have histologically or cytologically proven prostate cancer and radiologic evidence of metastatic disease. Progressive disease was mandatory and defined as two serially increasing PSA levels obtained more than one week apart with castration serum testosterone levels of < 50 ng/dl. Exclusion criteria included those patients with central nervous system metastases, patients with preexisting pleural or pericardial effusions, and managedcareoncology.com 41 patients who had received previous or ongoing therapy with cytotoxic chemotherapy or glucocorticoids. Patients were initially administered dasatinib 100 mg orally twice a day. After 25 patients received dasatinib at that dose, the dose was reduced to 70 mg orally twice a day due to clinical observation that the drug was equally effective but less toxic at the lower dose. The primary objective of the study was a composite response rate defined as either confirmed ≥ 50% PSA decline, stable disease (SD), complete response (CR), partial response (PR), or confirmed disappearance of lesion(s) by radionuclide bone scan assessment. Secondary endpoints included investigator assessment of changes in the bone scan, PSA, and bone turnover marker urinary N-telopeptide (uNTX). Safety of dasatinib in this patient population was also assessed. Results: Forty-seven patients were enrolled in the study; 25 initially received dasatinib 100 mg orally twice a day, and 22 initially received dasatinib 70 mg orally twice a day. The predefined endpoint of com- posite response/stable disease was achieved in 13 of 47 patients, or 28% (95% confidence interval, 16% to 43%). This exceeded the minimum expected response of 10%. Lack of progression was noted in 20 patients (43%) at week 12 and nine patients (19%) at week 24. Response rates were similar in both dosing arms. Of 41 evaluable patients, 21 (51%) achieved a ≥ 40% reduction in uNTX by week 12, and 33 (80%) had some reduction during the study. Of 40 patients evaluated, bone alkaline phosphatase was reduced in 24 patients (60%) at week 12, and 25 patients (63%) achieved some reduction while on the study. The most common adverse events were diarrhea (62%), nausea (47%), and fatigue (45%). The incidence of pleural effusions (any grade) was reported in 51% of those treated while pericardial effusions (grade 1 only) were noted in 23% of patients. There was no significant difference based upon daily dose of dasatinib received. Conclusion: This study provides initial evidence of dasatinib activity in 42 managedcareoncology Quarter 1 2010 patients with metastatic CRPC and bone disease. The therapy is reasonably well-tolerated in this chemotherapy-naive patient population. Managed Care Implications: Drug therapy with new mechanisms of action, such as dasatinib, may be a new option for patients with metastatic CRPC. Additional studies including combination therapy with dasatinib will further identify the role of this agent. Title: Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of CRPC. Authors: Attard G, Reid AHM, A’Hern R, et al. Reference: J Clin Oncol. 2009;27:37423748. Purpose: Patients who experience relapse from hormone-refractory or androgen-independent prostate cancer may respond to further hormonal treatments, but response rates are modest. There is evidence that CRPC remains hormonally driven by using adrenal hormones or through intracrine synthesis. CYP17 is a key to androgen and estrogen synthesis. Weak, nonspecific inhibitors of CYP17, such as ketoconazole (Nizoral), have shown some antitumor activity in CRPC. A more potent, selective, and irreversible inhibitor of CYP17, abiraterone, has shown promising activity in chemotherapynaive patients with CRPC. Methods: All patients were chemotherapy-naive with a diagnosis of progressive CRPC and had an ECOG performance status of 0 or 1. Patients were required to have documented progressive disease and a minimum washout period of four weeks after hormonal therapy (except luteinizing hormone-releasing hormone) and six weeks after stopping bicalu- tamide (Casodex) or nilutamide (Nilandron). Patients who had received previous cytotoxic chemotherapy or radiopharmaceuticals for treatment of their prostate cancer were excluded. One thousand milligrams of oral abiraterone acetate powder were administered once daily, continuously, to fasted patients in 28-day cycles. Computed tomography scans were performed every 12 weeks, and circulating tumor cell (CTC) enumeration was also performed. The primary objective of the study was the number of patients with a ≥ 50% decline in their PSA level after 12 weeks of therapy with abiraterone acetate. A secondary endpoint was drug safety. Results: Forty-two patients were enrolled in this phase 2 open-label, single-arm study. A decline in PSA of ≥ 50% was observed in 28 of 42 patients (67%), and declines of ≥ 90% were noted in eight (19%) patients. Radiologic responses were reported in nine (37.5%) patients. All were PRs. The median time to PSA progression (TTPP) was 225 days (range 162 to 287 days). The median TTPP for patients who had a ≥ 50% decline in PSA was 253 days (median 122 to 383 days) and 393 days in those patients with a ≥ 90% decline in PSA (range 252 to 533 days). Decreases in CTC counts from ≥ 5 to < 5/7.5 ml were noted in 10 of 59 (59%) patients, and 12 of 17 (70%) patients had a decline of ≥ 30% after the start of treatment. Abiraterone acetate was welltolerated. Secondary mineralocorticoid excess was noted in a majority of patients, manifested by hypokalemia, hypertension, and fluid overload. It was managed by the use of the oral-selective aldosterone blocker eplerenone (Inspra). Conclusion: CYP17 blockade by abiraterone acetate results in declines of PSA and CTC counts as well as radiologic responses as first-line therapy in the treatment of patients with metastatic CRPC. This confirms that CRPC commonly remains a hormone-driven disease. Managed Care Implications: New oral drug therapy with agents such as abiraterone acetate may have an important role to play in patients with metastatic CRPC. Additional studies will help to identify the exact role of such agents. Title: Integrated data from two randomized double-blind, placebo-controlled phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Authors: Higano CS, Schellhammer PF, Small EJ, et al. Reference: Cancer. 2009;115:36703679. Purpose: Prostate cancer is the most common solid tumor and second leading cause of cancer-related deaths in men in the U.S. Many men will experience disease control after primary therapy, but 20% to 40% of these patients will have a disease recurrence. While androgen deprivation will usually control these relapses, these patients will progress most likely to bone and/or regional lymph nodes. Management of androgen-independent prostate cancer (AIPC) is challenging. New agents with acceptable toxicity spectrums are needed. Sipuleucel-T is an autologous active cellular immunotherapy designed to stimulate an immune response against prostate cancer. It consists of autologous peripheral blood mononuclear cells, including antigen-presenting cells (APCs), which have been activated in vitro with a recombinant fusion protein. This protein is composed of prostatic acid phosphatase (PAP), an antigen linked to granulocyte-macrophage colony stimulating factor (GM-CSF, Leukine), an immune cell activator. Phase 1 and 2 studies show sipuleucel-T to be well-tolerated and to provide PSA responses as well managedcareoncology.com 43 as several objective responses. The purpose of these phase 3 trials was to validate those results. Methods: Data from two identically designed randomized, double-blind, placebo-controlled studies were combined to evaluate the safety and efficacy of sipuleucel-T. Patients had to have histologically proven adenocarcinoma of the prostate with radiologic evidence of metastases, serum testosterone level of < 50 ng/dl, and a life expectancy of at least three months. Also required were an ECOG PS of 0 or 1, (+) immunohistochemical for PAP in at least 25% of the tumor cells, adequate end-organ function, and a CD4+ T count of > 400/µL. Any prior therapy (chemotherapy, hormonal, radiation, or herbal) had to be discontinued at least four weeks before the start of the study. The only exception was luteinizing hormone-releasing hormone antagonists. Radiopharmaceuticals could not have been administered within 12 months of the trial. Patients were randomized in a 2:1 ratio to receive sipuleucel-T or placebo. After randomization, both groups underwent three leukapheresis procedures at weeks zero, two, and four with infusion of sipuleucel-T or placebo two days following the last leukapheresis. The primary objective of the study was to compare time to disease progression in patients with asymptomatic metastatic hormonerefractory prostate cancer between the two groups. Secondary endpoints included OS and drug safety. Results: Two hundred and twenty-five patients were randomized between the two studies. One hundred and forty-seven were treated with sipuleucel-T and 78 with placebo. Baseline characteristics were compa- Managed Care Implications: Immunotherapy may be another option for patients with AIPC. Given its favorable toxicity profile, sipuleucel-T in combination with other form(s) of therapy may be possible. rable between the two groups. Five patients treated with sipuleucel-T had a PSA reduction of ≥ 50%, and two patients had a PSA reduction of ≥ 25% for an overall PSA response rate of 4.8%. No patients in the placebo group had a confirmed PSA reduction of 25% or more. The median survival was 23.2 months for the sipuleucel-T vs. 18.8 months for those receiving placebo, showing a 21% reduction in the risk for disease progression (HR, 1.26; p = 0.111) and a 33% reduction in the risk for death in patients treated with the immunotherapy (HR, 1.50; p = 0.011). The percentage of patients alive at 36 months was 33% and 15%, again favoring the group treated with sipuleucel-T. The most common adverse events associated with treatment were chills, pyrexia, headache, dyspnea, vomiting, and tremor. These events were primarily grade 1 and 2 and usually lasted less than two days. Conclusion: The study demonstrates a survival benefit for patients treated with immunotherapy in comparison to placebo. That coupled with a modest toxicity profile suggests a favorable risk-benefit ratio for sipuleucel-T in patients with advanced prostate cancer. 44 managedcareoncology Quarter 1 2010 Title: Changes in alkaline phosphatase levels in patients with prostate cancer receiving degarelix or leuprolide: results for a 12-month comparative phase 3 study. Authors: Schroder FH, Tombal B, Miller K, et al. Reference: Br J Urol Int [published online ahead of print November 13, 2009]. Purpose: The bone is the most frequent site of metastases in men with prostate cancer. Bone formation and resorption are both altered in this patient population. Bone matrix components are released into the circulation during bone formation and resorption. Markers for bone formation include serum osteocalcin, procollagen I extension peptides, total serum alkaline phosphatase (S-ALP), and bone-specific alkaline phosphatase (B-ALP). Elevated S-ALP and B-ALP levels have been associated with progression of skeletal metastases in patients with prostate cancer and have been shown to be predictors of early death. Androgendeprivation therapy (ADT) is commonly used in patients with advanced prostate cancer and bony mets. The most commonly used agents to treat the disease are GnRH receptor agonists that achieve castrate testosterone levels, ≤ 0.5 ng/dl in nearly all patients. However, ADT with GnRH receptor agonists is associated with a decrease in bone mineral density and an increased risk for fracture. GnRH receptor blockers are a new class of hormonal therapy that induces a faster suppression of serum testosterone without causing a testosterone surge. Degarelix (Firmagon) is a GnRH receptor blocker that has shown activity in patients with prostate cancer who require ADT. This study compares the changes in S-ALP in patients with prostate cancer when treated with degarelix or leuprolide (Lupron). Methods: Men ages 18 and older with a histologically confirmed diagnosis of adenocarcinoma of the prostate for whom endocrine treatment was indicated were eligible. Patients were required to have a screening testosterone level of > 1.5 ng/dl and an ECOG PS of ≤ 2. Patients considered to be candidates for curative therapy were excluded. Patients were randomized to receive degarelix at a starting dose of 240 mg SQ, followed by monthly maintenance doses of 80 mg SQ (arm 1) or 160 mg SQ (arm 2) or leuprolide 7.5 mg IM monthly (arm 3). Therapy continued for 12 months. Antiandrogens were allowed in the leuprolide treatment for the prevention of a testosterone flare reaction at the discretion of the treating physician. S-ALP and PSA levels were measured at baseline and periodically during the study. The primary objective of the trial was to determine which drug suppressed S-ALP levels most effectively. Results focused on the comparison of degarelix 240/80 mg with leuprolide 7.5 mg, which were the doses approved by the FDA and European Medicines Agency. Results: Baseline characteristic and demographics were comparable between the three treatment arms. Six hundred and ten patients were included with a median age of 73 years and a median PSA level of 19 ng/dl. Two hundred and seven patients were treated with degarelix 240/80 mg and 201 with leuprolide 7.5 mg. Baseline S-ALP levels were high in patients with metastatic disease due to the presence of skeletal metastases and highest in patients with metastatic disease and hemoglobin levels < 13 g/dl at baseline. S-ALP levels were suppressed below baseline with degarelix but were maintained around baseline with leuprolide. A late rise in S-ALP was noted in the leuprolide-treated patients that was not noted with those treated with degarelix. The pattern of S-ALP response was similar in patients with a baseline PSA ≥ 50 ng/dl. Conclusion: Patients with metastatic prostate cancer with a baseline PSA ≥ 50 ng/dl and requiring ADT had a greater reduction in S-ALP levels when treated with degarelix than leuprolide. S-ALP suppression was noted throughout the study period in those treated with degarelix, which was not noted in patients treated with leuprolide. This suggests that degarelix may offer better S-ALP control and prolong control of skeletal metastases in this patient population. Managed Care Implications: GnRH receptor blockers, such as degarelix, may become the drugs of choice when treating patients with prostate cancer requiring ADT. Additional studies to verify these results are needed. Title: Docetaxel-based chemotherapy with zoledronic acid and prednisone in hormone refractory prostate cancer: factors predicting response and survival. Authors: Nayyar R, Sharma N, and Gupta NP. Reference: Int J Urol. 2009;16:726-731. Purpose: Androgen-deprivation therapy is the first-line treatment for metastatic prostate cancer with an average duration of response of 18 to 24 months. Treatment of hormone-refractory prostate cancer (HRPC) remains palliative. Docetaxel (Taxotere) is a potent inhibitor or microtubular depolymerization and has been managedcareoncology.com 45 shown to be active in the treatment of HRPC. The combination of docetaxel/prednisone has shown a survival advantage over mitoxantrone (Novantrone)/ prednisone in a multicenter trial. Zoledronic acid (Zometa) is a bisphosphonate that reduces pain and skeletal complications associated with bone metastases. It has several mechanisms of action, including inhibition of osteoblastic proliferation, inhibition of bone destruction through osteoclasts, and inhibition of production of prostaglandins E2 and interleukin 1. The purpose of this study was to combine docetaxel, prednisone, and zoledronic acid in patients with HRPC and identify prognostic factors predicting response to chemotherapy and improved survival. Methods: Men ages 45 to 85 with a histologically confirmed diagnosis of adenocarcinoma of the prostate with radiologic evidence of meta- static disease and disease progression after prior hormonal therapy were eligible. Patients were also required to have a Karnosky performance status (PS) of 60% to 100% and adequate end-organ function. A baseline physical exam, blood tests including PSA, radiologic imaging, and a bone scan were obtained. A baseline pain score was also documented using a numeric pain intensity scale. Docetaxel 75 mg/m2 IV and zoledronic acid 4 mg/m2 IV were administered every three weeks until disease progression or unacceptable toxicity. An 8 mg dose of IV dexamethasone was given with the chemotherapy, and prednisone was prescribed at a dose of 5 mg orally twice a day for the next five days. The primary endpoints of the study were either death of the patient or disease progression. Secondary endpoints included a reduction in pain score as defined by a minimum two-point decline in pain score from baseline 46 managedcareoncology Quarter 1 2010 without an increase in analgesics, or a reduction of ≥ 50% in analgesic intake without an increase in pain score and toxicity or the regimen. Results: Forty-four patients were enrolled and received a total of 274 cycles of chemotherapy (mean 6.3; range 2 to 21). The average PSA at baseline was 171.2 ng/dl (median 40.5 ng/dl; range 5.8 to 1,422.7 ng/dl). Good PSA response, more than 50% fall from baseline, was seen in 26 of 44 cases (59.1%) and partial response (25% to 50% fall in PSA) in 11 of 44 cases (25%). Those responses were maintained for a median of 10.6 months. Patients who received more than four cycles of chemotherapy had improved survival (p < 0.01). Median OS was 62.4 weeks, with patients with a good and partial PSA response achieving the best OS. A more than 75% reduction in pain score was noted in 31 of 44 patients (70.5%) with a more than 75% decrease in analgesic intake reported in 28 of 44 cases (63.6%). A more than 50% reduction in the activity of the bone scan was noted in 32 of 44 cases (72.7%). The most significant factors predicting survival via univariate Cox regression analysis were a Gleason score < 7 and the number of cycles of chemotherapy received. Adverse reactions were considered acceptable and consisted of myelosuppression, nausea, vomiting, diarrhea, and rash. Conclusion: The combination of docetaxel/prednisone/zoledronic acid is both safe and effective in the management of HRPC. Patients with a Gleason score < 7, a PSA decline of > 50%, and those who receive at least four cycles of chemotherapy have significantly better survival. Managed Care Implications: Early identification of patients with lower Gleason scores and significant declines in PSA is essential in determining long-term survival in patients with HRPC treated with this new drug combination. Title: Phase 1/2 study of docetaxel, gemcitabine, and prednisone in castrate-refractory metastatic prostate cancer. Authors: Buch-Hansen TZ, Bentzen L, Hansen S, et al. Reference: Can Chemo Pharm [published online ahead of print October 31, 2009]. Purpose: Most men with prostate cancer have disease that is initially responsive to hormonal therapy, although the majority become insensitive to this type of therapy over time. Chemotherapy then becomes the treatment of choice. Castrate-refractory metastatic prostate cancer (CRMPC) is defined as clinical disease progression and/ or an increase in PSA in spite of castrate levels of plasma testosterone. Patients with CRMPC often suffer from skeletal pain, fractures, and spinal cord compression, thus making palliation an important parameter of treatment. Docetaxel (Taxotere) has demonstrated improvement in OS and quality of life in this patient population and has become the cornerstone for chemotherapy regimens. The combination of docetaxel, gemcitabine (Gemzar), and prednisone has been shown to be active in other solid tumors including breast cancer and non-small-cell lung cancer. The purpose of this study was to assess the efficacy and toxicity of a fixed dose of docetaxel and prednisone with escalating doses of gemcitabine (DGP) in patients with CRMPC. Methods: This was an open-label multicenter phase 1/2 study. Eligible patients had histologically documented adenocarcinoma of the prostate with either radiologic or clinical evidence of metastatic disease and castrate levels (< 0.5 nmol/l) of testosterone. CRMPC was defined as clinical and biochemical progression despite castration. PSA levels had to be at least 10 µcg/l, and no previous treatment with estrogen or steroids for metastatic disease was allowed. End-organ function was required to be adequate, and patients had to have an ECOG PS of ≤ 2 and a life expectancy of at least three months. In phase 1, 15 patients were included, three at each dosing level of DGP. All received docetaxel 75 mg/m2 IV every three weeks and prednisone 5 mg orally twice a day continuously. The maximum tolerated dose of gemcitabine was 1,000 mg/m2 IV days one and eight of an every-21-day cycle. The primary endpoint of the phase 2 portion of the study was PSA response as defined as a ≥ 50% reduction in PSA from baseline, verified by a second measurement at least four weeks later. Secondary endpoints were time to progression (TTP) and toxicity. Results: Fifty patients were entered in the phase 2 portion of the trial. Thirty-seven patients (74%) achieved a biochemical response with a reduction in PSA by ≥ 50%. A major PSA response, as defined as a ≥ 75% reduction in PSA, was seen in 23 patients (46%). Single-agent docetaxel studies in the same patient population have shown 50% PSA response rates to range from 30% to 70%. The TTP was 7.9 months, and the OS was 13.9 months. OS in the single-agent docetaxel study, TAX 327, was 18.9 months. Twenty-four patients had measurable disease, with 12 (50%) achieving a partial response and five (21%) having stable disease. Neutropenia was the most common adverse event and developed in 74% of patients treated. Nonhematologic toxicity was mild. Conclusion: The PSA response rate was promising with the DGP combination, and adverse events were manageable. However, OS rates were comparable to single-agent docetaxel. Managed Care Implications: New chemotherapy regimens for the treatment of men with CRMPC are needed. The combination of DGP should not be considered since the PSA response rates and OS are similar to those achieved with singleagent docetaxel. managedcareoncology.com 47 regulatory and reimbursement Consultations: Where Do You Want to Go Next? by Roberta L. Buell, Managing Partner, Sausalito Healthcare Partners, and Principal Content Development, E-Expert Reimbursement Partners In the 2010 final Medicare physician fee schedule, the Centers for Medicare & Medicaid Services (CMS) announced that Medicare no longer pays Medicare Part B consultation codes for dates of service after January 1, 2010. 48 managedcareoncology Quarter 1 2010 Now, CMS directs providers to report other evaluation management (E/M) codes in lieu of these consultation codes. The question for many specialists is: Will commercial payors and managed care organizations follow suit? So far, most commercial insurers are continuing to pay for consultations. But will this continue? Should it continue? To ascertain the answer, we should undertake an analysis to determine why Medicare eliminated consults in the first place, what it is doing in terms of coding and payment, and how this fits or does not fit with nongovernment payors. We will outline those points herein. WHY MEDICARE ELIMINATED CONSULTATIONS: A HISTORICAL PERSPECTIVE For many years, Medicare has looked at consultations as an area of abuse by referring and consulting physician relationships. There was a flurry of investigations about husband-wife referrals and mutual consult “back scratching” in the 1990s. Governmental concerns increased again when the Office of Inspector General performed a study in 2004 that showed consults were increasing and were often not billed correctly.1 Medicare reimbursement for consultations increased from $3.3 billion in 2001 to $4.1 billion in 2004. Further, since 1992, CMS had not made policy changes that would affect the incidence of consultation payment errors from 2001 to 2004, suggesting that something was in fact wrong. To understand the situation better for this analysis, Medicare audited 400 consultations from 2001, extrapolated the results, and allegedly allowed approximately $1.1 billion more in 2001 than it should have for services that were billed as consultations. Approximately 75% of services billed as consultations and allowed by Medicare in 2001 did not meet all applicable program requirements, resulting in $1.1 billion in improper payments. Services billed as consultations often did not meet Medicare’s definition of a consultation (19%, $191 million), were billed as the wrong type or level of consultation (47%, $613 million), or were not substantiated by documentation (9%, $260 million). Consultations billed at the highest billing level (the most complex services, which generate the highest reimbursements under the physician fee schedule) and follow-up inpatient consultations were particularly problematic; approximately 95% of which were miscoded. So in response to this reported overpayment, two things occurred. First, the American Medical Association (AMA) changed the consult code definitions and eliminated follow-up consultations in the hospital. These changes allegedly instigated a Medicare Change Request (Transmittal 788, CR 4215) at the end of 2005 that changed the definition of consultations for Medicare patients. The change in definition differed from guidelines outlined by the AMA. Areas of contention were the definition of a transfer of care versus a consultative relationship and what constitutes a shared or split visit. Shared visits were and are common practices for many specialists. Fifty-one specialty and advocacy societies wrote CMS and asked it to rescind or clarify this change in definition and documentation. No response to these societies ever came from Medicare. Since that time, CMS has been debating with the AMA’s Current Procedural Terminology (CPT) Editorial Panel regarding the appropriate reporting of consultation codes. CMS has argued that physicians do not use consultation codes managedcareoncology.com 49 properly. Specific areas of disagreement include the physician’s responsibility for documentation of a referral and issues surrounding transfer of care. The AMA refused to amend its rules, until it was too late. In 2009, Highmark performed an audit on the highest level of consultation billing (Level 5) and found a 90% error rate. Thus, in July, Medicare proposed to stop paying for consults altogether. Last year, the AMA decided to clarify parameters for transfer of care and documentation of a referral. It did this, and along with many specialty societies, tried to lobby to stop Medicare’s elimination of consult payment. This effort was not successful, and despite opposition, CMS decided to stop making payments for consultation services starting January 1, 2010. WHAT’S GOING ON RIGHT NOW? In place of the consultation codes, CMS increased the work relative value units (RVUs) for new and established office visits, increased the work RVUs for initial hospital and initial nursing facility visits, and incorporated the increased use of these visits into the practice expense (PE) and malpractice calculations. CMS also increased the incremental work RVUs for the E/M codes that are built into the 10-day and 90-day global surgical codes. Despite these modifications, there is concern that this policy will have a negative impact on reimbursement to specialists. The risk to commercial payors is that these RVU increases may have a negative impact on private payors who use 2010 Medicare RVUs for these services and, at the same time, continue to pay for consultations. Providers do not report the following CPT codes on or after January 1, 2010: ■ Office consultation for a new or established patient (99241, 99242, 99243, 99244, and 99245) ■ Inpatient consultation for a new or established patient (99251, 99252, 99253, 99254, and 99255) CMS has preserved telehealth (G0425, G0426, and G0427) consultations to provide the ability for practitioners to provide and bill for initial inpatient consultations delivered via telehealth in areas where specialty services are not available. In place of consults, CMS directs providers to report E/M visit codes instead of consultation codes. Medicare has not provided specific coding crosswalks from consultation codes to existing E/M codes. And as a coding expert, I do not support the use of crosswalks since the services do not really have a one-to-one ratio and the individual services may be more complex than the “matching” code represents, causing underpayments. Providers should code a patient evaluation and management visit with E/M codes that represent where the visit occurs and identify the complexity of the visit performed in terms of the history, physical, and medical decision making performed, unless counseling time dominates the visit. Providers should report the following CPT codes for consultation services: Hospital outpatient/office. In the office or other outpatient setting where an evaluation is performed, physicians should report new and established office/ outpatient visit codes (CPT codes 9920199215) depending on the complexity of the visit and whether the patient is a new or established patient of that physician. 50 managedcareoncology Quarter 1 2010 The major difference between consults and office visits is that a code demarcates new versus established patients. By CPT definition, a new patient is “one who has not received any professional services from the physician, or another physician of the same specialty who belongs to the same group practice, within the past three years.” In contrast, an established patient has received professional services from the physician or another physician in the same group and the same specialty within the prior three years. Unless payor policies differ, for this purpose, hematology, hematology/oncology, medical oncology, and radiation oncology are considered separate specialties. The code criteria for established patients (99212-99215) are much less restrictive than consults of the same coding levels, meaning providers who use a crosswalk for these may lose money. Hospital inpatient and nursing facility setting. For the hospital inpatient and nursing facility setting, providers are directed to report initial hospital care visit codes (CPT codes 99221-99223) or nursing facility visit codes (CPT codes 99304-99306). The principal physician of record (usually the admitting physician) will append modifier “AI” Principal Physician of Record to the E/M code when billed. This modifier will identify the physician who oversees the patient’s care from all other physicians who may be furnishing specialty care. Subsequent inpatient consults will be reported as subsequent visit codes (CPT codes 99231-99233), as they have been since 2006. SELECTING THE RIGHT CODES IN 2010 As mentioned, CMS has not provided crosswalks from the eliminated con- sultation codes to existing visit codes. CMS has instructed physicians to select the code for the service based upon the content of the service. Medicare has noted that in order for physicians to bill the highest levels of visit codes, the services furnished must meet the definition of the code (e.g., to bill a Level 5 new patient visit, there must be a comprehensive history and physical, plus complex decision making). The specified duration of the visit is an ancillary factor and does not control the level of the service to be billed unless more than 50% of the face-toface time (for noninpatient services) or more than 50% of the floor time (for inpatient services) is spent providing counseling/coordination of care. The greatest confusion in this area is with inpatient consultation services. While for outpatient/office consultation services providers will be going from five consultation codes to five E/M visit codes, in the inpatient setting, providers experience a much more material change: They are going from five consultation codes to three initial visit codes. There may be confusion regarding reporting Level 1 and 2 inpatient consultation codes (CPT codes 99251 and 99252). These codes do not meet the minimum criteria for a Level 1 initial inpatient visit code. It has been advised by some Medicare intermediaries that providers should report an unlisted code for the lower levels. This code is 99499. Reporting of an unlisted code, which requires manual (as opposed to electronic billing) claim submission and documentation, hardly seems worth the effort for a lower level of service. Perhaps this is Medicare’s intent. That’s the bad news. The good news for specialists is that according to Medicare’s instructions, in the inpatient hospital setting and nursing facility setting, any physicians and qualified nonphysician practitioners (NPPs) who perform an initial evaluation may bill an initial hospital care visit code (CPT code 99221-99223) or nursing facility care visit code (CPT 99304-99306), where appropriate. This was not true with the historical consultation codes, where there had to be a request from another physician for a new problem. Further, CMS says in its instruction: “Medicare may pay for an inpatient hospital visit or an office or other outpatient visit if one physician or qualified NPP in a managedcareoncology.com 51 group practice requests an evaluation and management service from another physician in the same group practice when the consulting physician or qualified NPP has expertise in a specific medical area beyond the requesting professional’s knowledge.” These services would have almost certainly been billed with subsequent hospital visits (99231-99233) previously. USE OF PROLONGED SERVICES The elimination of consultation codes may raise questions regarding the appropriate use of prolonged visit codes. Prolonged visit codes are add-on codes billed with the primary E/M service. As an add-on code, these codes cannot be reported independently but must always be reported in addition to another E/M code. Prolonged visit codes are reported when treating patients whose symptoms are espe- cially complex and concerning and the provider finds himself or herself spending significantly more time with the patient. Prolonged visit codes 99354 and/or 99355 can be billed with the office or other outpatient setting E/M codes. Prolonged visit codes 99356 and/or 99357 are billed with the inpatient setting E/M codes. CMS has established minimum threshold times to determine if the prolonged service can be reported. Physicians may count only the duration of direct faceto-face contact between the physician and the patient (whether the service was continuous or not) beyond the typical/average time of the visit code billed to determine whether prolonged services can be billed and to determine the prolonged services codes that are allowable. Medicare’s updated instruction for the use of these codes may be due to the fact that the inpatient and outpatient codes that are being used in lieu of consultations have by definition lower time descriptors. Thus, prolonged service codes may be appended more often due to these lower time descriptors for face-to-face physician time due to counseling, coordination of care, or unusual medical circumstances. WHAT PRIVATE PAYORS AND MCOS SHOULD DO Most of the oncology practices in our client base have reported that, with the exception of Medicare Advantage and Medi-Gap plans, the majority of payors are continuing to pay for consultations as described in CPT. Should payors continue to pay for them or follow Medicare guidelines? Let’s look at the issues. 1. Ease of Use: Obviously, if you take note of everything outlined above, this is not an easy change to imple- 52 managedcareoncology Quarter 1 2010 ment. Based on my experience with physician billing, there are probably thousands of rejected Medicare claims resulting from these new changes. These claims will be appealed or rebilled, creating administrative expense on both sides. In addition, through its intermediaries, Medicare has sponsored various live and Webbased workshops to explain the conversion of consult codes. However, the continuous misinterpretation of these rules is inevitable and could create unexpected administrative expense that obfuscates anticipated savings. 2. Savings: Medicare claims that this change is “budget-neutral,” meaning it has nothing to gain. If this were true, there would be no reason to make the change. After all, CMS’s original hypothesis was that it was paying too much for these services. We conducted an analysis of the costs of switching physician Medicare coding of consults to E/M visits, and this analysis shows a revenue reduction of $5,000 to $15,000 per provider depending upon the level and volume of consults. However, if there is any movement in the level of coding in terms of higher levels, prolonged services, or a significant uptick in hospital evaluations, budget “neutrality” might actually come to fruition for the Medicare program, which was clearly not its monetary objective. 3. Claims Data Tracking: For capitated plans and closed preferred provider organizations, it is important to see how many referrals are made from the primary care physician (PCP) to specialists throughout an illness. Consult codes demonstrate referrals made and how many specialists are treating patients. Moreover, the billing of consults can be evidence of arrangements such as cross-referrals, whereby medically unnecessary referrals are made between husband-wife teams and friendly physicians within a community. Without these tracking mechanisms, utilization of high-level E/M services may skyrocket. Removal of these codes may have some unintended consequences for the Medicare program. But these consequences will be much more unlikely in a coordinated care payment world. 4. Loss of Plan Specialists: Let’s be clear: Oncologists are not dropping out of the Medicare program because consults have been removed. The patient load is too great so that few can afford to walk away from Medicare. But for smaller plans with fewer patients in treatment, this can happen, particularly if the reimbursement and gatekeeping are unsatisfactory to the oncology group. Every plan must have oncologists on its panel and, in some communities, there is just not a lot of choice. Thus, it is our view that Medicare made its decision based upon years of analysis that demonstrated miscoding and possible abuse. There were other resolution strategies for this issue. But the fact remains that Medicare went with the change that was implemented. Private payors need to be aware of the intricacies of consultation omission and how these will impact them operationally, strategically, and fiscally in the short and long terms. FURTHER INFORMATION For further details and information, CMS has released two articles about this new policy that you may wish to review: ■ Revisions to consultation services payment policy. Medicare Learning Network. MLN Matters Article #MM6740. www.cms.hhs. gov/MLNMattersArticles/downloads/ MM6740.pdf. ■ CMS manual system: pub 100-04 Medicare claims processing, transmittal #1875. www.cms. hhs.gov/transmittals/downloads/ R1875CP.pdf. Reference: 1. Levinson D. Consultations in Medicare: coding and reimbursement. Office of Inspector General. March 2006 OEI-09-02-00030. http://oig.hhs.gov/oei/reports/ oei-09-02-00030.pdf. Accessed February 3, 2009. managedcareoncology.com 53 resources & references This resource guide features prostatecancerspecific, oncologyrelated links and Web sites that may be of use to the reader in daily practice.* American Cancer Society (ACS). CancerNet. This Web site from The ACS is a national, community-based voluntary health organization with state divisions and more than 3,400 local offices. The organization offers programs for education, patient service, advocacy, and rehabilitation. From the home page, select prostate cancer under “Learn About Cancer” for a detailed guide that contains information on risk factors, diagnosis, staging, and treatment. www.cancer.org the ASCO provides peer-reviewed information on prostate cancer, including clinical trials, staging, treatment, illustrations, and current research. www.cancer.net/patient/Cancer+Types/ Prostate+Cancer American Society of Clinical Oncology (ASCO). This nonprofit organization founded in 1964 is committed to improving cancer care and prevention, advancing the education of physicians and other health professionals in the care of cancer patients, supporting cancer research, and fostering communication among cancer-related subspecialties. It also seeks to assist oncologists in addressing the challenges in their practice. The Web site below offers clinical tools, abstracts, articles, and other resources for treating prostate cancer. http://prostateca.asco.org MedlinePlus. A service of the U.S. National Library of Medicine and the U.S. National Institutes of Health, this Web site offers links to peer-reviewed articles and abstracts on prostate cancer, clinical trial information, glossaries, statistics, and much more. www.nlm.nih.gov/medlineplus/ prostatecancer.html National Cancer Institute. The National Cancer Institute, part of the U.S. National Institutes of Health, conducts and supports research, training, health information dissemination, and other programs with respect to the cause, diagnosis, and prevention of cancer. This online guide provides information on treatment, screening, testing, and clinical trials, plus links to published literature and research on prostate cancer. www.cancer.gov/cancertopics/types/ prostate National Comprehensive Cancer Network (NCCN). The NCCN is a nonprofit alliance of 21 cancer centers. The NCCN’s primary goal is to improve the quality, effectiveness, and efficiency of oncology practices. It publishes clinical practice guidelines that are developed and updated through an evidence-based process. This Web site outlines the practice guidelines for prostate cancer. Users must register to access guidelines. www.nccn.org/professionals/ physician_gls/f_guidelines.asp OncoLink Information and Resources. OncoLink’s mission is to provide patients, healthcare professionals, and the public with accurate, cancer-related information. Started by University of Pennsylvania cancer specialists in 1994, this Web site includes information on treatment, clinical trials, and other resources for prostate cancer. www.oncolink.org/types/article. cfm?c=16&s=57&ss=608&id=8039 Prostate Cancer Foundation (PCF). Founded in 1993, the PCF focuses on finding better treatments and a cure for prostate cancer. The foundation is a world leader in funding prostate cancer research. The PCF’s Web site includes information on diagnosis, treatment, clinical trials, and grants. www.prostatecancerfoundation.org *Note: Magellan/ICORE Healthcare does not endorse or verify the information presented. 54 managedcareoncology Quarter 1 2010 7TH ANNUAL Oncology Summit SAVE THE DATE! SEPTEMBER 10, 2010, NEW yORk CITy A CONFERENCE FOR ALL INDUSTRY LEADERS ATTENDEE OBjECTIVES • Gaininsightintosuccessfulpayorreimbursement approaches • Understandtheimpactoftheoncologypipeline overthenext12to24months • Assesstheopportunitiesandchallengesassociated withoralchemotherapyandtreatmentvariability • Integratethemedicalandpharmacybenefitsto providecomprehensiveoncologybenefits • Measuretheeconomicsinusingchemotherapy, chemosupport,andhospice • IdentifyandaddressemployerandMedicareneeds MORE DETAILS TO COME! For more information, please e-mail us at [email protected]. WHO SHOULD ATTEND? • Healthplanexecutiveswhoarechargedwith themanagementoftheirplan’soncology drug-relatedcosts • Oncologypracticemanagerswithprivate payorreimbursementresponsibilities • Distributorsandspecialtypharmacieswho areconcernedwiththedynamicsin chemotherapyaccessanddistribution • Pharmaceuticalmanufacturerswhoofferinfused ororaloncologyproductsormanufacturerswho wishtounderstandcurrentandfutureoncology managementstrategies ICORE HEALTHCARE 5850 T.G. Lee Blvd., Suite 510 Orlando, FL 32822 866-664-2673 www.icorehealthcare.com Delivering on the promise of biotechnology through collaboration. Access Partnership Experience Value Care Visit the Medical Professionals page at Amgen.com to find out how we’re delivering on the promise of biotechnology. © 2010 Amgen Inc. All rights reserved. MC41878-B