Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial

Abstract

BACKGROUND: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. PATIENTS AND METHODS: We conducted post-hoc hypothesis-generating analysis of SOLO-2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to next progression/death. RESULTS: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than olaparib arm: 12.1 vs. 6.9 months (hazard ratio [HR] 2.17; 95% CI 1.47-3.19). Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13; 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (N = 96), TTSP was significantly longer in the placebo arm: 14.3 vs. 7.0 months (HR 2.89; 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (N = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 vs. 6.0 months (HR 1.58; 95% CI 0.86-2.90). CONCLUSION: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2 mutated patients with PSROC compared to patients not previously receiving PARPi. The optimal strategy for patients who relapse after PARP inhibitors is an area of ongoing research