Report Back from SGO: What's the Latest in Ovarian Cancer?
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The report discusses developments in ovarian cancer treatment, highlighting the prevalence and mortality rates in the U.S. It emphasizes the role of PARP inhibitors in extending the time to cancer recurrence for women with BRCA mutations, while also noting the limited benefits of adding immunotherapy to existing treatments. New therapies targeting gas6/axl signaling are also in development, indicating ongoing research in improving ovarian cancer outcomes.
Report Back from SGO: What's the Latest in Ovarian Cancer?
- 1. 1 Report Back from SGO: What’s the Latest in Ovarian Cancer? Joyce F. Liu, MD, MPH Associate Chief and Director of Clinical Research, Division of Gynecologic Oncology, Dana-Farber Cancer Institute May 7, 2021
- 2. 2 Disclosures • Advisory board: AstraZeneca, Clovis, Genentech, GSK, Merck, Regeneron • Research Funding (to DFHCC): 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, CytomX Therapeutics, GlaxoSmithKline, Regeneron, Surface Oncology, Tesaro, Vigeo Therapeutics
- 3. 3 Ovarian Cancer 2021 • 21,410 new cases and 13,770 deaths annually in US • 5th leading cause of cancer death for women in US Siegel, Cancer Statistics 2021 13,770
- 4. 4 Ovarian Cancer Treatment 2021 Initial diagnosis and treatment 1st recurrence 2nd recurrence 3rd recurrence … Surgery Chemotherapy Chemotherapy ?Surgery Chemotherapy Chemotherapy … How do we make ovarian cancer treatment more effective? • How can we improve initial treatments to prevent or delay disease recurrence? • Can immunotherapy improve treatments for women with ovarian cancer? • What are the novel therapeutic targets that can provide new treatment options?
- 5. 5 Improving initial treatment – maintenance therapy Initial diagnosis and treatment Surgery Chemotherapy 1st recurrence Add additional therapy to prevent or delay disease recurrence? Maintenance Therapy 1st recurrence
- 6. 6 Maintenance therapy with bevacizumab GOG-218 ICON7 Burger, N Engl J Med 2011 Perren, N Engl J Med 2011
- 7. 7 Maintenance therapy with bevacizumab GOG-218 ICON7 Burger, N Engl J Med 2011 Perren, N Engl J Med 2011 Bevacizumab maintenance can delay cancer recurrence but does not help women live longer. FDA-approved as maintenance therapy for newly diagnosed ovarian cancer.
- 8. 8 PARP inhibitor maintenance therapy Silver and Iglehart, N Engl J Med, 2009
- 9. 9 Four trials of PARP inhibitor maintenance in newly diagnosed ovarian cancer SOLO1 PRIMA PAOLA1 VELIA Moore et al., N Engl J Med 2018 Gonzalez-Martin et al., N Engl J Med 2019 Ray-Coquard et al., N Engl J Med 2019 Coleman et al., N Engl J Med 2019 PARP inhibitor maintenance can delay cancer recurrence in newly diagnosed ovarian cancer. Activity is highest in women with a BRCA1 or BRCA2 mutated cancer.
- 10. 10 SGO Update: 5 year follow-up of olaparib maintenance in women with BRCA-mutated ovarian cancer (SOLO1) Bradley et al., SGO 2021 Annual Meeting
- 11. 11 SGO Update: 5 year follow-up of olaparib maintenance in women with BRCA-mutated ovarian cancer (SOLO1) • Newly diagnosed advanced ovarian cancer • BRCA mutation • Response to chemotherapy R 2:1 Olaparib x 2 years Placebo x 2 years
- 12. 12 SGO Update: 5 year follow-up of olaparib maintenance in women with BRCA-mutated ovarian cancer (SOLO1) End of treatment Continued benefit! Bradley et al., SGO 2021 Annual Meeting
- 13. 13 SGO Update: SOLO1 5 year follow-up takeaways • Benefit from PARP inhibitor maintenance remains at 5 year follow-up for women with a BRCA-mutated ovarian cancer • Testing for BRCA mutation in newly diagnosed ovarian cancer is important • We do not yet know if this will help women live longer • The long-term benefit for PARP inhibitor maintenance for women without a BRCA mutation is not currently known
- 14. 14 SGO Update: Adding immunotherapy to chemotherapy and bevacizumab in newly diagnosed ovarian cancer: IMagyn050 Landen et al., SGO 2021 Annual Meeting
- 15. 15 Adding immunotherapy to chemotherapy in ovarian cancers JAVELIN Ovarian 100: Chemo+avelumab vs chemo 1L JAVELIN Ovarian 200: PLD+avelumab vs PLD 2-3L Ledermann et al., SGO 2020 Annual Meeting Pujade-Lauraine et al., SGO 2019 Annual Meeting Adding immunotherapy to chemotherapy without benefit in ovarian cancer to date.
- 16. 16 SGO Update: Adding immunotherapy to chemotherapy and bevacizumab in newly diagnosed ovarian cancer: IMagyn050 • Newly diagnosed advanced ovarian cancer • No previous treatment R 1:1 Chemotherapy + bevacizumab + placebo Chemotherapy + bevacizumab + atezolizumab Bevacizumab + placebo maintenance Bevacizumab+ atezolizumab maintenance
- 17. 17 SGO Update: Adding immunotherapy to chemotherapy and bevacizumab in newly diagnosed ovarian cancer: IMagyn050 Landen et al., SGO 2021 Annual Meeting; Presented by Moore et al., ESMO 2020 Adding immunotherapy to upfront ovarian cancer treatment does not appear to have benefit. True across different biomarkers, including BRCA status.
- 18. 18 SGO Update: PARP inhibitors in recurrent ovarian cancer: ARIEL4 Kristeleit et al., SGO 2021 Annual Meeting
- 19. 19 SGO Update: PARP inhibitors in recurrent ovarian cancer: ARIEL4 • Recurrent ovarian cancer • BRCA mutation • At least 2 prior chemotherapies for ovarian cancer • No prior PARP inhibitor R 2:1 Rucaparib Standard chemotherapy • Paclitaxel (if within 12 months of last platinum) • Platinum-based chemotherapy (if >12 months after last platinum)
- 20. 20 SGO Update: PARP inhibitors in recurrent ovarian cancer: ARIEL4 Kristeleit et al., SGO 2021 Annual Meeting
- 21. 21 SGO Update: ARIEL4 Takeaways • ARIEL4 confirms the activity of PARP inhibitors in PARP inhibitor naïve recurrent BRCA-mutated ovarian cancer • Rucaparib had improved activity over chemotherapy (with some caveats) • For a woman with BRCA-mutated ovarian cancer who has not yet received PARP inhibitor, this should be considered as a possible option
- 22. 22 SGO Update: PARP inhibitor maintenance in recurrent ovarian cancer: NOVA final analysis Matulonis et al., SGO 2021 Annual Meeting
- 23. 23 SGO Update: PARP inhibitor maintenance in recurrent ovarian cancer: NOVA final analysis Matulonis et al., SGO 2021 Annual Meeting; First reported Mirza et al., N Engl J Med 2016
- 24. 24 SGO Update: PARP inhibitor maintenance in recurrent ovarian cancer: NOVA final analysis Need to be cautious in interpreting these trial results – data were incomplete Matulonis et al., SGO 2021 Annual Meeting
- 25. 25 SGO Update: PARP inhibitor maintenance in recurrent ovarian cancer: NOVA final analysis Niraparib maintenance therapy did not help women live longer, although there was a trend towards benefit in women with a BRCA mutation Matulonis et al., SGO 2021 Annual Meeting
- 26. 26 SGO Update in Context: PARP inhibitor maintenance in BRCA-mutated ovarian cancers (SOLO2) All patients Adjusted for subsequent PARPi therapy 12.9 mo improvement 16.9 mo improvement SOLO2 and NOVA long-term results support PARP inhibitor maintenance for women with BRCA-mutated ovarian cancer who are PARP inhibitor naïve. Poveda et al., ASCO 2020 Virtual Meeting
- 27. 27 SGO Update: New therapies on the horizon – AVB-500 and targeting GAS6/AXL signaling
- 28. 28 SGO Update: AVB-500 and targeting GAS6/AXL signaling Fuh et al., SGO 2021 Annual Meeting Scaltriti, Elkabets, Baselga Clin Can Res 2016 Cell proliferation Cell survival
- 29. 29 SGO Update: AVB-500 and targeting GAS6/AXL signaling Fuh et al., SGO 2021 Annual Meeting
- 30. 30 SGO Update: AVB-500 and targeting GAS6/AXL signaling Fuh et al., SGO 2021 Annual Meeting
- 31. 31 GOG-3059: Weekly paclitaxel +/- AVB-500 in recurrent platinum-resistant ovarian cancer Schema courtesy of Katherine Fuh
- 32. 32 SGO 2021 Updates • PARP inhibitors are an active and important part of our armamentarium against ovarian cancer • Most active in women with BRCA-mutated cancers • Prolonged benefit in newly diagnosed disease for BRCA-mutated ovarian cancer, even after PARP inhibitor therapy has been stopped • Activity in recurrent disease • More work is needed to understand how to effectively leverage immunotherapy in ovarian cancer • Novel therapies such as targeting of GAS6/AXL continue to be developed
- 33. 33 Questions?