Olaparib Plus Bevacizumab Leads to Improvement in Progression-Free Survival in BRCA-Mutated Ovarian Cancer

The combination of olaparib plus bevacizumab lead to a potentially meaningful improvement in progression-free survival (PFS) versus olaparib alone in women with BRCA-mutated newly diagnosed ovarian cancer. The study findings were presented in conjunction with the Society for Gynecological Oncology 2020 Annual Meeting on Women’s Cancer.

The goal of the study was to assess the comparative efficacy of olaparib with bevacizumab versus without bevacizumab, olaparib versus bevacizumab, and bevacizumab versus placebo in the maintenance treatment of newly-diagnosed advanced ovarian cancer with BRCA mutation.

An unanchored population-adjusted indirect comparison (PAIC) was performed on the endpoint of PFS, according to the study authors, using individual patient data from the SOLO1 phase 3 trial. Inverse probability of treatment weights was used to match each arm of PAOLA-1 to the SOLO1 cohort, such that key baseline clinical and demographic characteristics were similar across populations.

All analyses were performed in patients with complete baseline data. Weighted Cox regression analysis was performed to estimate the comparative efficacy of different treatment strategies and was supplemented by weighted Kaplan-Meier analyses.

Data for 380 patients with complete baseline data from SOLO1 (n=254 olaparib, n=126 placebo) were pooled with data from 222 patients who were BRCA-mutated with complete baseline data in PAOLA-1 (n=151 olaparib plus bevacizumab, n=71 bevacizumab plus placebo). Prior to matching, PFS at 2 years was 76% with olaparib plus bevacizumab, 73% with olaparib, 44% with bevacizumab, and 36% with placebo. The weights allocated to the PAOLA-1 cohort ranged from 0.12 to 3.98, with an effective sample size of 166. The matched PAOLA-1 cohort had baseline data comparable to SOLO1, with 85% FIGO stage 3, 81% complete response after first-line chemotherapy, and 75% no residual disease after surgery.

According to the study authors, despite matching, the results of the analysis should be viewed with the limitation that it is a nonrandomized comparison. The relative clinical benefit of bevacizumab appears to be additive and consistent across regimens, and its use leads to a similar level of benefit when combined with olaparib and compared with olaparib alone or used as monotherapy and compared with placebo, according to the study.

Reference

• Population adjusted indirect comparison of the SOLO1 and PAOLA-1/ENGOT-ov25 studies of olaparib with or without bevacizumab, bev alone and placebo in the maintenance treatment of women with newly diagnosed stage III/IV ovarian cancer with BRCA mutation. SGO website. https://sgo.confex.com/sgo/2020/meetingapp.cgi/Paper/16926 . Accessed April 14, 2020.