Advanced Ovarian Cancer in Practice An Expert Commentary

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

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, nurse practitioners, physician assistants, pharmacists, and other healthcare professionals involved in the management of advanced ovarian cancer.

Activity Learning Objective Upon successful completion of this educational program, participants should be able to: 
 l Review the relevance and significance of the activity in the broader context of clinical care. 


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CME Information: Physicians l Credit for Family Physicians Med. Page Today "News-Based CME" has been reviewed and is acceptable for up to 2098 Elective credits by the American Academy of Family Physicians. AAFP accreditation begins January 1, 2012. Term of approval is for one year from this date. Each article is approved for 0. 5 Elective credits. Credit may be claimed for one year from the date of each article.

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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 to this educational activity. The staffs of Projects In Knowledge and Med. Page Today have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

Ovarian Cancer l l l 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 l l l Months l 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

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

CA 125 -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 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 l An estimated 75% to 85% of ovarian cancer patients have advanced-stage disease at diagnosis. l The five-year survival for early disease (stage I) is 94% compared with 46% for all patients with ovarian cancer. l Optimal surgical debulking followed by adjuvant chemotherapy remains the standard of care for patients with advanced ovarian cancer. l Standard first-line systemic therapy is the combination of a platinum agent and a taxane. l Intraperitoneal chemotherapy is recommended, having demonstrated a survival advantage over intravenous delivery. l Adverse events are more common and potentially more severe with intraperitoneal chemotherapy, but strategies exist to minimize these effects.

SUMMARY (cont. ) l l 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. ) l l l 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 CA 125 testing has not been shown to improve survival. However, the decision to use CA 125 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.