Download Targeted Therapy in Recurrent Ovarian Cancer

Advanced Ovarian Cancer in Practice
An Expert Commentary With
Justin Chura, MD, MBA
A Clinical Context Report
Clinical Context:
Advanced Ovarian Cancer in Practice
Expert Commentary
Jointly Sponsored by:
and
Clinical Context:
Advanced Ovarian Cancer in Practice
Expert Commentary
This activity is supported in part by an
educational grant from
Genentech BioOncology
Advanced Ovarian Cancer
Clinical Context Series
The goal of this program is to provide upto-date information and multiple
perspectives on the pathogenesis,
symptoms, risk factors, and complications
of advanced ovarian cancer as well as
current and emerging treatments and best
practices in the management of advanced
ovarian cancer.
Advanced Ovarian Cancer
Clinical Context Series
Target Audience
Oncologists, hematologists,
obstetricians/gynecologists, primary care
physicians, nurses, nurse practitioners,
physician assistants, pharmacists, and
other healthcare professionals involved in
the management of advanced ovarian
cancer.
Activity Learning Objective
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Discussant
Justin Chura, MD
Director, Robotic Surgery
Associate Director, Gynecologic Oncology
Department of Obstetrics and Gynecology
Division of Gynecologic Oncology
Crozer-Keystone Health Network
Upland, Pennsylvania
Disclosure Information
Justin Chura, MD
has disclosed that he has no relevant financial
relationships or conflicts of interest to report.
Disclosure Information
Vandana G. Abramson, MD, Assistant Professor of
Medicine, Vanderbilt University School of Medicine,
Nashville, Tenn.; Charles Bankhead; and Dorothy Caputo,
MA, RN, BC-ADM, CDE, Nurse Planner, have disclosed that
they have no relevant financial relationships or conflicts of
interest with commercial interests related directly or indirectly
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The staffs of Projects In Knowledge and MedPage Today
have no relevant financial relationships or conflicts of interest
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educational activity.
Ovarian Cancer






22,000 new cases annually
15,000 deaths annually
Overall survival:
75% at 1 year
46% at 5 years
38% at 10 years
Five-year survival after early diagnosis: 94%
Only 15%-25% of cases diagnosed early
Advanced disease: stage III to stage IV
Source: American Cancer Society, National Comprehensive
Cancer Network
Standard Chemotherapy Regimens
For Advanced Ovarian Cancer
IV paclitaxel + IP cisplatin
IV paclitaxel + IV carboplatin
IV docetaxel + IV carboplatin
Source: National Comprehensive Cancer Network
Intraperitoneal vs Intravenous Chemotherapy
Findings from GOG 172




N=415
Stage III ovarian or primary peritoneal cancer
Optimal surgery (<1 cm residual tumor mass)
Randomization:
IV paclitaxel + IV cisplatin
Or
IV paclitaxel + IP cisplatin + IP paclitaxel
100.0
IV therapy
Months
80.0
65.6
60.0
49.7
40.0
20.0
IP therapy 2
18.3
23.8
0.0
Median progression-free survival
Median overall survival
Findings from GOG 172
Grade 3-4 Adverse Events (%)
IV
IP
P
Leukopenia
64
76
<0.001
Low Platelets
4
12
0.002
Gastrointestinal
24
46
<0.001
Renal/Genitourinary
2
7
0.03
Neurologic
9
19
0.001
Fever
4
9
0.02
Infection
6
16
0.001
Fatigue
4
18
<0.001
Metabolic
7
27
<0.001
Pain
1
11
<0.001
Hepatic
<1
3
0.05
Other
<1
3
0.05
Therapy For Recurrent/Relapsed
Ovarian Cancer
Platinum Sensitive (platinum-free interval ≥6 months)
Combinations
Carboplatin
+ paclitaxel
Carboplatin
+ weekly paclitaxel
Carboplatin
+ docetaxel
Carboplatin
+ gemcitabine
Carboplatin
+ liposomal doxorubicin
Cisplatin
+ gemcitabine
Single agents
Carboplatin
Cisplatin
Source: National Comprehensive Cancer Network
THERAPY FOR
RECURRENT/RELAPSED OVARIAN
CANCER (cont.)
Platinum Resistant (platinum-free interval <6 months)

Docetaxel

Oral etoposide

Gemcitabine

Liposomal doxorubicin

Weekly paclitaxel

Topotecan
Source: National Comprehensive Cancer Network
OCEANS: Targeted Therapy in
Recurrent Ovarian Cancer
Randomized Treatment
Carboplatin + Gemcitabine + Placebo X 6 to 10 cycles
Placebo continued until progression
Or
Carboplatin + Gemcitabine + Bevacizumab X 6 to 10
cycles
Bevacizumab maintenance continued until progression
OCEANS: Targeted Therapy in
Recurrent Ovarian Cancer
Results
Placebo
Bevacizumab
P
Progression-free survival (mo.)
8.4
12.4
<0.001
Objective response (%)
57.4
68.5
<0.0001
Median response duration (mo.)
7.4
10.4
<0.0001
Interim overall survival (mo.)
29.9
35.5
0.094
CA125-Guided Trial of Immediate
versus Delayed Therapy
Results
E
D
N
265
264
Time to second-line treatment (mo.)
0.8
5.6
Median follow-up (mo.)
56.9
56.9
Time to third-line Rx or death (mo.)
12.5
17.1
<0.0001
Median survival (mo.)
25.7
27.1
0.85
Source: Lancet 2010; 376:1155-1163.
P
<0.00001
SUMMARY

An estimated 75% to 85% of ovarian cancer patients have
advanced-stage disease at diagnosis.

The five-year survival for early disease (stage I) is 94%
compared with 46% for all patients with ovarian cancer.

Optimal surgical debulking followed by adjuvant chemotherapy
remains the standard of care for patients with advanced ovarian
cancer.

Standard first-line systemic therapy is the combination of a
platinum agent and a taxane.

Intraperitoneal chemotherapy is recommended, having
demonstrated a survival advantage over intravenous delivery.

Adverse events are more common and potentially more severe
with intraperitoneal chemotherapy, but strategies exist to
minimize these effects.
SUMMARY (cont.)


Treatment for relapsed or recurrent ovarian cancer is additional
chemotherapy, possibly following additional surgery.
The choice of systemic therapy for relapsed or recurrent ovarian
cancer depends on the interval from first-line therapy,
commonly called the platinum-free interval. Recurrence within
six months of first-line therapy is considered platinum-resistant
and generally not responsive to additional platinum-based
chemotherapy. A platinim-free interval of six months or greater
defines platinum-sensitive disease and platinum-based
chemotherapy is included among the options for second-line
and subsequent lines of chemotherapy.
SUMMARY (cont.)



Currently, no targeted therapy has an approved indication for
advanced ovarian cancer. However, bevacizumab has
demonstrated potential to improve outcomes when used in
conjunction with conventional chemotherapy.
Monitoring patients with CA125 testing has not been shown to
improve survival. However, the decision to use CA125
monitoring should be left to the discretion of the patient and
treating physician.
A critical need exists for a means to diagnose more patients
with early-stage disease.