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For Decision Makers in Managed Care
Quarter 1 2010
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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
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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
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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
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Published by:
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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
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managedcareoncology.com 3
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Today, he got the cancer treatment he needed.
Along with a healthy dose of peace of mind.
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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.
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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
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Orlando, FL 32822
866-664-2673
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