Primary results of a randomized phase 3 trial indicate that prolonged treatment with bevacizumab for up to 30 months does not provide survival benefit in patients with advanced ovarian cancer; therefore, bevacizumab treatment duration of 15 months remains the standard of care in this setting.
A multicenter, open-label, randomized, 2-arm phase 3 trial (NCT01462890) evaluated the optimal treatment duration of bevacizumab combined with carboplatin/paclitaxel chemotherapy in patients with advanced ovarian cancer. Primary results of this study were reported at the 2021 American Society of Clinical Oncology Annual Meeting.
The trial enrolled patients with histologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer, with International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IV, and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, who underwent debulking surgery ≤8 weeks before treatment initiation, and >4 weeks before first bevacizumab dose. Eligible patients received 6 cycles of chemotherapy (paclitaxel 175 mg/m2 plus carboplatin AUC 5, every 3 weeks) plus bevacizumab (15 mg/kg every 3 weeks). Patients were randomized (1:1) to receive bevacizumab for either 15 months (Bev15 arm) or 30 months (Bev30 arm). Stratification was achieved by FIGO stage/residual tumor (stage IIB-IIIC/no residual tumor vs stage IIB-IIIC/residual tumor or stage IV). The primary end point was investigator-assessed progression-free survival (PFS); secondary end points were overall survival, objective response rate, quality of life, safety, and tolerability. The trial was designed with 80.2% (0.82) power to detect a hazard ratio of 0.66, favoring experimental treatment after 697 PFS events.
From November 2011 to August 2013, 927 women were randomized in the study; of these, 464 were assigned to the Bev15 arm, and 463 patients to the Bev30 arm. Baseline characteristics were balanced between arms, and the median age was 61 years. The majority of patients had epithelial ovarian cancer (83%), high-grade serous histology (79%), ECOG PS 0 or 1 (96%), and no residual tumor (58%).
At a median follow-up of 85 months, no significant difference was noted in PFS between the Bev15 and Bev30 arms (median PFS, 24.2 vs 26.0 months). Similarly, no significant differences were seen in subgroup analyses of PFS, when stratified by FIGO IIB-IIIC with or without residual tumor, or FIGO IV. Safety data were consistent with those previously described for bevacizumab, with the emergence of no new safety signals with prolonged treatment.
Primary results of this trial indicate that although prolonged treatment with bevacizumab for up to 30 months is feasible, it does not provide survival benefit in patients with advanced ovarian cancer. Therefore, bevacizumab treatment duration of 15 months remains the standard of care in this setting.
Source: Pfisterer J, Joly F, Kristensen G, et al. Optimal treatment duration of bevacizumab (BEV) combined with carboplatin and paclitaxel in patients (pts) with primary epithelial ovarian (EOC), fallopian tube (FTC) or peritoneal cancer (PPC): a multicenter open-label randomized 2-arm phase 3 ENGOT/GCIG trial of the AGO Study Group, GINECO, and NSGO (AGO-OVAR 17/BOOST, GINECO OV118, ENGOT Ov-15, NCT01462890). J Clin Oncol. 2021;39(suppl_15). Abstract 5001.