1. Advanced Ovarian Cancer in Practice An Expert Commentary With Justin Chura, MD, MBA A Clinical Context Report

2. Jointly Sponsored by: and Clinical Context: Advanced Ovarian Cancer in Practice Expert Commentary

3. This activity is supported in part by an educational grant from Genentech BioOncology Clinical Context: Advanced Ovarian Cancer in Practice Expert Commentary

4. Advanced Ovarian Cancer Clinical Context Series The goal of this program is to provide up- to-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.

5. 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.

6. Activity Learning Objective

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12. 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 Discussant

13. Disclosure Information Justin Chura, MD has disclosed that he has no relevant financial relationships or conflicts of interest to report.

14. Disclosure Information and have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. 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 to this educational activity. and have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. The staffs of Projects In Knowledge and MedPage Today have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

15. Source: American Cancer Society, National Comprehensive Cancer Network 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

16. Standard Chemotherapy Regimens For Advanced Ovarian Cancer IV paclitaxel + IP cisplatin IV paclitaxel + IV carboplatin IV docetaxel + IV carboplatin Source: National Comprehensive Cancer Network

17. 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 Months

18. Findings from GOG 172 Grade 3-4 Adverse Events (%) IVIPP Leukopenia6476<0.001 Low Platelets4120.002 Gastrointestinal2446<0.001 Renal/Genitourinary270.03 Neurologic9190.001 Fever490.02 Infection6160.001 Fatigue418<0.001 Metabolic727<0.001 Pain111<0.001 Hepatic<130.05 Other<130.05

19. 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

20. 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

21. 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

22. OCEANS: Targeted Therapy in Recurrent Ovarian Cancer Results PlaceboBevacizumabP Progression-free survival (mo.)8.412.4<0.001 Objective response (%)57.468.5<0.0001 Median response duration (mo.)7.410.4<0.0001 Interim overall survival (mo.)29.935.50.094

23. CA125-Guided Trial of Immediate versus Delayed Therapy Results EDP N265264 Time to second-line treatment (mo.)0.85.6<0.00001 Median follow-up (mo.)56.9 Time to third-line Rx or death (mo.)12.517.1<0.0001 Median survival (mo.)25.727.10.85 Source: Lancet 2010; 376:1155-1163.

24. 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.

25. 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.

26. 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.