Advanced Ovarian Cancer in PracticeAdvanced Ovarian Cancer in Practice

An Expert Commentary With An Expert Commentary With Justin Chura, MD, MBAJustin Chura, MD, MBA

A Clinical Context ReportA Clinical Context Report

Jointly Sponsored by:Jointly Sponsored by:

andand

Clinical Context: Clinical Context: Advanced Ovarian Cancer in PracticeAdvanced Ovarian Cancer in Practice

Expert CommentaryExpert Commentary

This activity is supported in part by an This activity is supported in part by an educational grant from educational grant from

Genentech BioOncologyGenentech BioOncology

Clinical Context: Clinical Context: Advanced Ovarian Cancer in PracticeAdvanced Ovarian Cancer in Practice

Expert CommentaryExpert Commentary

Advanced Ovarian Cancer Advanced Ovarian Cancer Clinical Context SeriesClinical Context Series

The goal of this program is to provide up-The goal of this program is to provide up-to-date information and multiple to-date information and multiple perspectives on the pathogenesis, perspectives on the pathogenesis, symptoms, risk factors, and complications symptoms, risk factors, and complications of advanced ovarian cancer as well as of advanced ovarian cancer as well as current and emerging treatments and best current and emerging treatments and best practices in the management of advanced practices in the management of advanced ovarian cancer.ovarian cancer.

Advanced Ovarian Cancer Advanced Ovarian Cancer Clinical Context SeriesClinical Context Series

Target AudienceTarget Audience

Oncologists, hematologists, Oncologists, hematologists, obstetricians/gynecologists, primary care obstetricians/gynecologists, primary care physicians, nurses, nurse practitioners, physicians, nurses, nurse practitioners, physician assistants, pharmacists, and physician assistants, pharmacists, and other healthcare professionals involved in other healthcare professionals involved in the management of advanced ovarian the management of advanced ovarian cancer.cancer.

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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

DiscussantDiscussant

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Justin Chura, MDJustin Chura, MD

has disclosed that he has no relevant financial has disclosed that he has no relevant financial relationships or conflicts of interest to report. relationships or conflicts of interest to report.

Disclosure InformationDisclosure InformationVandana G. Abramson, MD, Assistant Professor of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn.; Charles Bankhead; andand Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner, have disclosed that have disclosed that they have no relevant financial relationships or conflicts of they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly interest with commercial interests related directly or indirectly to this educational activity.to this educational activity.

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Source: American Cancer Society, National Comprehensive Cancer Network

Ovarian Cancer

22,000 new cases annually 15,000 deaths annually Overall survival:

75% at 1 year46% at 5 years38% at 10 years

Five-year survival after early diagnosis: 94% Only 15%-25% of cases diagnosed early Advanced disease: stage III to stage IV

Standard Chemotherapy Regimens

For Advanced Ovarian Cancer

IV paclitaxel + IP cisplatin

IV paclitaxel + IV carboplatin

IV docetaxel + IV carboplatin

Source: National Comprehensive Cancer NetworkSource: National Comprehensive Cancer Network

49.7

65.6

18.323.8

0.0

20.0

40.0

60.0

80.0

100.0

Median progression-free survival Median overall survival

IV therapy IP therapy 2

Intraperitoneal vs Intravenous ChemotherapyFindings 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

Mon

ths

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)

CombinationsCarboplatin + paclitaxelCarboplatin + weekly paclitaxelCarboplatin + docetaxelCarboplatin + gemcitabineCarboplatin + liposomal doxorubicinCisplatin + gemcitabine

Single agentsCarboplatinCisplatin

Source: National Comprehensive Cancer Network

THERAPY FOR RECURRENT/RELAPSED OVARIAN

CANCER (cont.)

Platinum Resistant (platinum-free interval <6 months)DocetaxelOral etoposideGemcitabineLiposomal doxorubicinWeekly paclitaxelTopotecan

Source: National Comprehensive Cancer Network

OCEANS: Targeted Therapy in Recurrent Ovarian Cancer

Randomized Treatment

Carboplatin + Gemcitabine + Placebo X 6 to 10 cyclesPlacebo continued until progression

Or

Carboplatin + Gemcitabine + Bevacizumab X 6 to 10 cyclesBevacizumab 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 P

N 265 264

Time to second-line treatment (mo.) 0.8 5.6 <0.00001

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.

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.