Robert E. Bristow, MD, MBA Professor and Director Division of Gynecologic Oncology University of California, Irvine – Me

1. Update on Ovarian Cancer Robert E. Bristow, MD, MBA Professor and Director Division of Gynecologic Oncology University of California, Irvine – Medical Center

2. Ovarian Cancer Center • Mission: • To provide exemplary and holistic clinical care to patients • with ovarian cancer. • To enhance community awareness of ovarian cancer regarding • the importance of early diagnosis and the benefits of • centralized expert care. • To advance the science of the prevention and treatment of • ovarian cancer in a meaningful way. Discover ▪ Teach ▪ Heal

3. Gynecologic Oncology Faculty Discover ▪ Teach ▪ Heal

4. Ovarian Cancer Center • Clinical Services - coordination of multidisciplinary care - prevention, early detection, cancer survivorship - surgery and regional therapeutics - chemotherapy and clinical trials - ancillary services • Community Outreach and Education - web-based platform - virtual support group survivor network - conferences - international visiting scholar program • Research and Discovery - molecular biology and translational science - healthcare outcomes Discover ▪ Teach ▪ Heal

5. Ann’s Clinic Screening, Early Detection, Cancer Survivorship High-risk patients - genetic counseling & testing - surveillance programs - cancer prophylaxis Cancer survivors - programmatic plan - psycho-social wellness - management of treatment toxicities Discover ▪ Teach ▪ Heal

6. Peritoneal Surface Malignancies  Disease confined to peritoneal cavity for much of natural history  Generally amenable to surgical resection  Positive survival impact of chemotherapy - varies by disease site Discover ▪ Teach ▪ Heal Discover ▪ Teach ▪ Heal

7. Radical Surgery for Ovarian Cancer Right Ovary Uterus Bladder Tumor Sigmoid Tumor Left Ovary Discover ▪ Teach ▪ Heal

8. Radical Surgery for Ovarian Cancer Uterus Bladder Tumor Cervix Distal Sigmoid Culdesac Tumor Discover ▪ Teach ▪ Heal

9. Radical Surgery for Ovarian Cancer Vaginal Cuff Rectosigmoid Colon Discover ▪ Teach ▪ Heal

10. Development of Intra-Peritoneal (IP) Chemotherapy 1950’s: First use of intraperitoneal chemotherapy for malignant ascites 1968: Long-term peritoneal access device 1978: Demonstration of slow peritoneal clearance of some drugs 1984: Feasibility of intermittent large volume intraperitoneal therapy 1996: First report of a survival benefit for IP vs. IV chemotherapy in advanced ovarian cancer Discover ▪ Teach ▪ Heal

11. Armstrong DK et al. NEJM 2006; 354:34. Discover ▪ Teach ▪ Heal

12. PFS: 18.3 vs 23.8 months OS: 49.7 vs 66.9 months Armstrong DK et al. NEJM 2006; 354: 34. Discover ▪ Teach ▪ Heal

13. (Optimal) (Optimal) Alkeran Cisplatin Paclitaxel IP Rx The ‘Evolution’ of Treatment for Advanced Ovarian Cancer and Effect on Survival Surgical & Chemotherapy Improvements (Suboptimal) Discover ▪ Teach ▪ Heal

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15. IP Therapy Discover ▪ Teach ▪ Heal

16. IP Therapy Discover ▪ Teach ▪ Heal

17. IP Therapy Discover ▪ Teach ▪ Heal

18. IP Therapy Discover ▪ Teach ▪ Heal

19. Primary Cytoreductive Surgery Contemporary Survival Outcomes Study Chemotherapy Residual Median Survival GOG152 IV-CDDP/IV-Taxol >1cm 36 months GOG172 IV-CDDP/IV-Taxol <1cm 50 months IP-CDDP/IV+IP-Taxol<1cm 67 months 0.1–1.0cm 39 months no gross 78 months 0.1–1.0cm 53 months no gross 127 months Rose PG et al. N Eng J Med 2004; 351: 2489. Armstrong DK et al. N Eng J Med 2006; 354: 34. Discover ▪ Teach ▪ Heal

20. Hyperthermia and Neoplasia Heat is…  Directly cytotoxic to cancer cells - disrupts microtubule system - induces primary protein damage - promotes vascular stasis  Synergistic with some chemotherapy agents Knox 1991, Stellar 1998 Discover ▪ Teach ▪ Heal Discover ▪ Teach ▪ Heal

21. HIPEC Schematic Discover ▪ Teach ▪ Heal Discover ▪ Teach ▪ Heal

22. HIPEC Techniques  Open (colisuem)  Closed Discover ▪ Teach ▪ Heal Discover ▪ Teach ▪ Heal

23. Role of HIPEC in Ovarian Cancer  Retrospective study design (1995-2005)  Advanced ovarian cancer (n=43)  Up-front HIPEC cisplatin + IV chemotherapy  Morbidity – 13.9%; mortality – 2.3%  Median OS = 53 months - complete initial resection = 131 months  Median PFS = 39 months Melis A et al. Bull Cancer 2011, doi 21659062. Discover ▪ Teach ▪ Heal Discover ▪ Teach ▪ Heal

24. Burger RA et al. NEJM 2011; 365: 2473. Discover ▪ Teach ▪ Heal

25. PFS: +3.8 month maintenance Rx OS: no significant effect Burger RA et al. NEJM 2011; 365: 2473. Discover ▪ Teach ▪ Heal

26. Fertility Preservation • Ovarian cancer - conservative surgery - young patients - early stage disease, atypical tumor types - chemotherapy with ovarian suppression Discover ▪ Teach ▪ Heal

27. Robotic Surgery ● daVinci surgical platform - patient-side robot - vision cart - robotic master console Advantages Improved visualization Finer instrument control and dexterity Ergonomic design Autonomous surgical environment Discover ▪ Teach ▪ Heal

28. da Vinci®– Robotic Surgery Technology Discover ▪ Teach ▪ Heal

29. Research and Discovery Clinical Trials • Ovarian cancer - intraperitoneal chemotherapy / HIPEC - molecular profiling - quality of life / cancer survivorship - developmental therapeutics / biologic agents Discover ▪ Teach ▪ Heal

30. Research and Discovery QOH Ovarian Cancer Research Laboratory • PhD recruitment underway • Collaborative effort • Genetic screening and early detection • Molecular basis of disease - characteristics of long-term survivors - circumventing chemo-resistance Discover ▪ Teach ▪ Heal

31. Research and Discovery •Surgical techniques • Advanced imaging techniques / onco-imaging •Clinical trials of new chemotherapeutic agents • Biological therapies • Public health applications Discover ▪ Teach ▪ Heal

32. Modern Approach to Cancer Therapeutics Research and Discovery Pathways Analysis Patient Metabolism Mutations Genes Downregulated Genes Upregulated Discover ▪ Teach ▪ Heal

33. OVA1  Qualitative serum test – 5 immunoassays - Apolipoprotein A - Transthyretin - 2 Microglobulin - Transferrin - CA125 II  Single numerical result: 0 - 10  FDA approved September 2009  Ovarian mass, > 18y/o, planned surgery  Triage tool for surgical decision-making  Not a screening or independent diagnostic test CategoryLow RiskHigh Risk Premenopausal <5.0 ≥5.0 Postmenopausal <4.4 ≥4.4 Discover ▪ Teach ▪ Heal

34. OVA1 Sensitivity vs CA125 Overall Performance Ueland F. et al. IntGyn Cancer Soc Annual Meeting, 2010, Prague. Discover ▪ Teach ▪ Heal

35. Disparities in Epithelial Ovarian Cancer Quality of Care and Survival According to Race and Socioeconomic Status: a Study of 47,160 Patients from the National Cancer Data Base Robert E. Bristowa, Matthew A. Powellb, Noor Al-Hammadic, Ling Chenc, J. Phillip Millerc, Phillip Y. Rolandd, David G. Mutchb, William A. Clibye aDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology University of California, Irvine School of Medicine bDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology cDepartment of Biostatistics Washington University in St. Louis School of Medicine dGynecologic Oncology, Department of Gynecology and Obstetrics Saint Francis Francis Hospital and Medical Center eDivision of Gynecologic Surgery, Department of Obstetrics and Gynecology Mayo Clinic Discover ▪ Teach ▪ Heal

36. Adherence to NCCN Guidelines Race 65.6% 61.5% 56.4% 51.3% 43.9% 35.6% *p<0.0001 * * * Discover ▪ Teach ▪ Heal

37. Adherence to NCCN Guidelines Payer * * * *p<0.0001 Discover ▪ Teach ▪ Heal

38. Adherent/Non-Adherent Care by Race 5-year Overall Survival Adherent White 41.4% Non-adherent White 37.8% Adherent African-American33.3% Non-adherent African-American 22.5% p<0.0001 N=47,160 Discover ▪ Teach ▪ Heal

39. Outreach and Education Public Community - Education and Awareness - Virtual support network Resource for Professionals - Education and Awareness - Expedited referral system - Partnering in patient care Discover ▪ Teach ▪ Heal

40. Thank you! Discover ▪ Teach ▪ Heal