Maintenance olaparib plus bevacizumab (bev) after platinum-based chemotherapy plus bev in patients (pts) with newly diagnosed advanced high-grade ovarian cancer (HGOC): Efficacy by BRCA1 or BRCA2 mutation in the phase III PAOLA-1 trial.

6039 Background: In PAOLA-1/ENGOT-ov25 (NCT02477644), adding the PARP inhibitor olaparib to maintenance bev after first-line platinum-based chemotherapy plus bev led to a statistically significant progression-free survival (PFS) benefit in pts with advanced HGOC (HR 0.59; 95% CI 0.49–0.72) (Ray-Coquard et al. 2019). Retrospective subgroup analysis in GOG-0218 (Norquist et al. 2018) suggested BRCA mutation (BRCAm) status did not significantly impact the PFS benefit provided by bev. We explored the efficacy of olaparib plus bev by BRCA1 mutation ( BRCA1m) or BRCA2 mutation ( BRCA2m) in PAOLA-1. Methods: PAOLA-1 is a randomized, double-blind, Phase III trial in pts with newly diagnosed, FIGO stage III–IV, high-grade serous or endometrioid OC, fallopian tube or primary peritoneal cancer receiving platinum-based chemotherapy plus bev then maintenance bev. Pts unrestricted by surgical outcome or BRCAm status and in response to first-line therapy were randomized to maintenance olaparib tablets (300 mg bid for up to 24 months) plus bev (15 mg/kg q3w for up to 15 months in total) or placebo plus bev, stratified by first-line treatment outcome and tumor BRCAm status. Investigator-assessed PFS (modified RECIST v1.1) by BRCAm was a predefined analysis. Results: Of 806 randomized pts, 160 (20%) had tumor BRCA1m, 76 (9%) had tumor BRCA2m and 1 (<1%) had both. Median PFS follow-up was 24.1 and 27.4 months in BRCA1m and BRCA2m pts, respectively. At primary data cutoff, PFS was prolonged with olaparib plus bev versus placebo plus bev in BRCA1m pts and BRCA2m pts (Table). The percentage of BRCA1m pts who received olaparib plus bev and were progression-free at 1 and 2 years was 95% and 73% (vs. 70% and 29% for placebo plus bev) and for BRCA2m pts was 89% and 84% (vs. 84% and 53%) (Kaplan-Meier estimates). Conclusions: In PAOLA-1, maintenance olaparib plus bev provided a significant PFS benefit versus placebo plus bev in all pts analysed, regardless of whether they had BRCA1m or BRCA2m. The median PFS in the control arm suggests a role for bev in this subgroup and the hazard ratio versus an active control arm shows the value of adding maintenance olaparib to bev. Clinical trial information: NCT02477644. [Table: see text]