Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): A final overall survival analysis of a multicenter, open-label, randomized, phase 3 trial.

person Rongyu Zang Institute for Ovarian Cancer, Fudan University, & Department of Gynecologic Oncology, Fudan University Zhongshan Hospital, Shanghai, China info_outline Rongyu Zang, Jianqing Zhu, Jihong Liu, Rong Jiang, Xi Cheng, Yulian Chen, Huixun Jia, Tingyan Shi, Yi Guo, Yanling Feng, Dongsheng Tu, Yuqin Zhang, Xiao Huang, Shiyang Jiang, Wen Gao, Huijuan Yang, Ping Zhang

Authors person Rongyu Zang Institute for Ovarian Cancer, Fudan University, & Department of Gynecologic Oncology, Fudan University Zhongshan Hospital, Shanghai, China info_outline Rongyu Zang, Jianqing Zhu, Jihong Liu, Rong Jiang, Xi Cheng, Yulian Chen, Huixun Jia, Tingyan Shi, Yi Guo, Yanling Feng, Dongsheng Tu, Yuqin Zhang, Xiao Huang, Shiyang Jiang, Wen Gao, Huijuan Yang, Ping Zhang Organizations Institute for Ovarian Cancer, Fudan University, & Department of Gynecologic Oncology, Fudan University Zhongshan Hospital, Shanghai, China, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China, Sun Yat-sen University Cancer Center, Guangzhou, China, Fudan University Zhongshan Hospital, Shanghai, China, Fudan University Cancer Hospital, Shanghai, China, Shanghai General Hospital, Shanghai, China, School of Public Health, Fudan University, Shanghai, China, Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China, Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada, Gynecologic Oncology Department, Fudan University Cancer Hospital, Shanghai, China Abstract Disclosures Research Funding Institute Background: Surgery for platinum-sensitive relapsed ovarian cancer is widely practiced but has contradictory outcomes of survival in previously published studies. Methods: This multicenter, open-label, randomized, phase 3 trial was performed in four primarily academic centers in China. Eligible patients were aged ≥18 years old with platinum-sensitive relapsed ovarian cancer and were predicted to have resectable disease according to the international model (iMODEL) combined with PET-CT, which was reported previously. Overall survival (OS) and progression-free survival were the co-primary end points in hierarchical testing and planned for the final analysis of OS with a two-sided alpha of 0.05, when 209 deaths happened. Results: Between July 19, 2012 and June 3, 2019, 357 patients were enrolled. Patients were randomly assigned to receive surgery (182 pts.) or control (175 pts.). Median follow-up was 82.5 m. The median OS was 58.1 m in the surgery group and 52.1 m in the control group (hazard ratio [HR] for death, 0.80; 95% confidence interval [CI], 0.61 to 1.05; P=0.109). Overall, 61/175 (35%) patients in the control group crossed to surgery in subsequent therapies. A sensitive analysis showed that adjusted HR for death for crossover to surgery was 0.76 (95% CI, 0.58 to 0.99) (Table). When excluding the center with the highest crossover rate, secondary cytoreduction provided a 21.0-m benefit of overall survival over a control therapy. The highest crossover surgery rate was 49% in patients with 4-19 sites of relapse. The hazard ratio for death in patients with 1-19 sites was 0.69 (95% CI, 0.46 to 1.03). Patients with a complete resection had the most favorable outcome, with a median OS of 73 m. Median time to second subsequent therapy was 34.8 m vs 28.1 m (HR 0.68; 0.55-0.87). 24 of 182 (13.2%) patients remained relapse free and alive over 60 m in the surgery group, as compared with 5 of 175 (0.6%) patients in the control group. Conclusions: Secondary cytoreduction did not increase overall survival in the intention-to-treat population but led to a longer duration of overall survival when the crossover effect was taken into consideration. These findings are arguably clinically meaningful and support the efficacy of secondary cytoreduction in specialized centers and selected patients. ClinicalTrial.gov: NCT01611766. Res Sponsor: Shanghai Gynecologic Oncology Group. Clinical trial information: NCT01611766. Surgery Control OS events, n/N (%) 101/182 (55) 109/175 (62) Median OS, m 58.1 52.1 36m OS, % 70 65 HR (95% CI) 0.80 (0.61-1.05) *The rank-preserving structure failure time model was used in adjusted OS.

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