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Robert L. Coleman, MD

This randomized controlled trial investigates the effectiveness of secondary cytoreductive surgery followed by chemotherapy, with or without bevacizumab, in platinum-sensitive, recurrent ovarian cancer. The study aims to determine if these treatment approaches increase overall survival in patients with ovarian cancer.

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Robert L. Coleman, MD

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  1. A Phase III Randomized Controlled Trial of Secondary Cytoreductive Surgery followed by Platinum-Based Combination Chemotherapy, With or Without Bevacizumab in Platinum-Sensitive, Recurrent Ovarian Cancer: Surgical Parameters A NRG Oncology-Gynecologic Oncology Group Study Robert L. Coleman, Nick M. Spirtos, Danielle Enserro, Thomas J. Herzog, Paul Sabbatini, Deborah Kay Armstrong, Byoung-Gie Kim, Keiichi Fujiwara, Joan L. Walker, Patrick J. Flynn, Angeles Alvarez Secord, David E. Cohn, Mark F. Brady, Robert S. Mannel Robert L. Coleman, MD

  2. Faculty Disclosure March 30 - April 2, 2014Sheraton Sonoma CountyPetaluma, California Off-Label Product Use

  3. GOG 213: Primary Objectives • Objective #1: To determine if the addition of BEVACIZUMAB to paclitaxel and carboplatin followed by maintenance bevacizumab will INCREASE OVERALL SURVIVAL relative to paclitaxel and carboplatin alone in patients with platinum-sensitive recurrent ovarian cancer – [Coleman et. al., Lancet Oncol 2017] • Objective #2: To determine if SECONDARY CYTOREDUCTION followed by chemotherapy will INCREASE OVERALL SURVIVAL in patients with platinum-sensitive recurrent ovarian cancer Robert L. Coleman, MD

  4. GOG 213: Primary Objectives • Objective #1: To determine if the addition of BEVACIZUMAB to paclitaxel and carboplatin followed by maintenance bevacizumab will INCREASE OVERALL SURVIVAL relative to paclitaxel and carboplatin alone in patients with platinum-sensitive recurrent ovarian cancer • Objective #2: To determine if SECONDARY CYTOREDUCTION followed by chemotherapy will INCREASE OVERALL SURVIVAL in patients with platinum-sensitive recurrent ovarian cancer [Coleman et. al., ASCO 2018, #5501] Robert L. Coleman, MD

  5. GOG 213: Schema Modification 8/29/2011 • Chemotherapy (2 options): • Paclitaxel 175 mg/m2 + • Carboplatin AUC5 • Gemcitabine 1000 mg/m2 d1,8 + • Carboplatin AUC5 • Bevacizumab (optional): • 15 mg/kg • Starting cycle 2 for post-op to a max of 8 cycles • Maintenance allowed until progression, intolerance or death • Cycle Length: 21 days PHYSICIAN CHOICE Robert L. Coleman, MD

  6. Eligibility for Surgery & Outcome • No specific eligibility criteria for surgical candidacy was provided • Assessment was to be made by physical exam, laboratory and imaging (MRI, PET/CT and/or CT) and individual physician experience • The goal of secondary cytoreduction is: • COMPLETE REMOVAL OF ALL VISIBLE DISEASE(CGR) • Surgical outcomes: (ITT population) • CGR = 64% (146/230) • 14 patients did not undergo surgery • Surgical outcomes (Per protocol population) • CGR = 68% (146/216) Robert L. Coleman, MD

  7. DSMC Activities • Primary endpoint: OS • Stratification variables: • Platinum-Free Interval (6-12, ≥12 months) • Chemotherapy regimen chosen (4 options) • Targeted adjusted HR: 0.70 (increase from 50% to 61.5% at 22 months) • Maturity for OS occurs at 250 deaths • DSMC performed an updated planned interim analysis in December 2017 • Events: 147/125 minimum (59% informative) • Based on a target HR: 0.70, the observed conditional power to achieve this effect was 0.1% Robert L. Coleman, MD

  8. Patient Characteristics Robert L. Coleman, MD

  9. Primary/Secondary Endpoints: Surgery vs. No Surgery Robert L. Coleman, MD

  10. Exploratory Endpoint: Prognostic Impact of CGR CGR CGR Non-CGR Non-CGR HR: 0.51 (0.36-0.72) HR: 0.67 (0.41-1.08) Robert L. Coleman, MD

  11. Exploratory Endpoint: CGR (68% of Surgical Patients) vs. Chemotherapy (All) CGR Chemotherapy CGR Chemotherapy HR: 0.68 (0.51-0.90) HR: 1.11 (0.74-1.66) Robert L. Coleman, MD

  12. Questions Raised From Primary Analysis What were the details of the surgery performed? How many had isolated vs diffuse disease? What were the post-operative complications? How did platinum-free interval and disease distribution impact surgical outcome? Was there any subgroup who benefitted from surgery? Robert L. Coleman, MD

  13. Surgical/Patient Characteristics Robert L. Coleman, MD

  14. Surgical/Patient Characteristics * 14 randomized patients did not undergo the procedure; 10 addn’l missing data Robert L. Coleman, MD

  15. Surgical Outcomes * 14 randomized patients did not undergo the procedure; 10 addn’l missing data Robert L. Coleman, MD

  16. Survival Outcomes: Survival by Disease Distribution Robert L. Coleman, MD

  17. Survival Outcomes: Survival by Distribution vs Chemo HRSurg 1-site vs. HRNoSurg: 0.64 (95%CI: 0.45-0.90) HRSurg “other” vs. HRNoSurg: 1.06 (95%CI: 0.82-1.37) HRSurg 1-site vs. HRNoSurg: 0.93 (95%CI: 0.58-1.48) HRSurg “other” vs. HRNoSurg: 1.58 (95%CI: 1.09-2.31) Robert L. Coleman, MD

  18. Survival Outcomes: Survival by Disease Distribution Robert L. Coleman, MD

  19. Survival Outcomes: Survival by Distribution & Chemo HRSurg 2-sites vs. HRNoSurg: 0.66 (95%CI: 0.49-0.88) HRSurg “other” vs. HRNoSurg: 1.28 (95%CI: 0.96-1.70) HRSurg 2-sites vs. HRNoSurg: 0.90 (95%CI: 0.59-1.36) HRSurg “other” vs. HRNoSurg: 2.03 (95%CI: 1.35-3.05) Robert L. Coleman, MD

  20. Survival: Impact of Platinum-Free Interval (PFI) Prognostic Impact of PFI Q2: 19.8 mos Q3: 28.2 mos Q4: 45.2 mos Q0: 8.3 mos Q1: 13.9 mos Quintile Robert L. Coleman, MD

  21. Survival: Impact of Platinum-Free Interval (PFI) Prognostic Impact of PFI Effect of Surgery by PFI Q2: 19.8 mos Q3: 28.2 mos Q4: 45.2 mos Q2: 19.8 mos Q3: 28.2 mos Q4: 45.2 mos Q0: 8.3 mos Q1: 13.9 mos Q0: 8.3 mos Q1: 13.9 mos Quintile Quintile Robert L. Coleman, MD

  22. Conclusions Secondary cytoreduction can be safely performed in women with platinum-sensitive recurrent ovarian cancer Complete gross resection was achieved in 68% of the per protocol population and was significantly higher (~79%) among women with preoperative oligometastatic disease (both 1 and 1-2 sites) Women with oligometastatic disease undergoing surgery had longer PFS and OS than those with greater preoperative tumor burden Platinum-free interval was prognostic for OS However...Neither patients with oligometastatic disease nor those with a long preoperative platinum-free interval has superior OS compared to chemotherapy alone The benefit of secondary cytoreduction in recurrent platinum-sensitive ovarian cancer remains undefined Robert L. Coleman, MD

  23. GOG-213: Special Acknowledgements • Study Co-Chairs: • Nick Spirtos, Danielle Enserro, Thomas J. Herzog, Paul Sabbatini, Deborah Kay Armstrong, Byoung Kim, Keiichi Fujiwara, Joan L. Walker, Patrick J. Flynn, Angeles Alvarez Secord, David E. Cohn, Mark F. Brady, Robert S. Mannel • NCI: • Elise Kohn, Helen Chen • Genentech: • Kathy Look, Amreen Husain • Member institutions • USA: 45 member institutions • Korean GOG • Japanese GOG • Patients and families who generously have participated or are participating in this trial

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