Efficacy and safety of olaparib according to age in BRCA-1/2 mutated patients with recurrent platinum-sensitive ovarian cancer: Analysis of the phase III SOLO2 (AGO-OVAR 2.23/ENGOT-Ov21) study.

Abstract

6068 Background: Adding olaparib as maintenance treatment to BRCA-1/2 mutated patients (pts) with recurrent platinum-sensitive ovarian cancer (PSOC) has significantly improved progression-free survival (PFS) as well as patient-centered endpoints. As BRCA mutated pts tend to be younger, specific information on efficacy and safety of olaparib for elderly pts is of special interest. Methods: 295 pts from the SOLO2 trial that randomly assigned to olaparib or placebo were categorized according to age cutoff at 65 years. The efficacy and tolerability of olaparib relative to placebo within in each age group was assessed based on PFS and toxicity outcomes. Quality of life (QoL) was assessed using EQ-5D-5L descriptive system score and FACT Trial Outcome Index (TOI) and evaluated using generalized estimating equations (GEE) and time without significant symptoms of toxicity (TWiST) analysis. Results: Baseline characteristics were similar in pts ≥65 years (N=62; 21%) compared to pts <65 years (N=233; 79%), except for more BRCA2 mutations in elderly pts (39% vs. 23%). There was no significant difference in the magnitude of PFS benefit from olaparib in elderly as compared with younger pts (interaction P=0.33). The PFS adjusted hazard ratio (HR) of olaparib vs. placebo arms were respectively HR≥65 0.43 (95%-confidence interval [CI] 0.24-0.81) and HR<65 0.31 (95%-CI 0.22-0.43). Elderly and younger pts also had comparable safety profiles with no significant differences in median time on olaparib treatment (≥65: 27 vs. <65: 33 months), percentage of pts experiencing at least one grade >2 adverse event with olaparib (≥65: 73% vs. <65: 79%), or requiring at least one dose interruption or dose reduction (≥65: 77.5 vs. <65: 77.6%). No differences were found with regards to QoL scores. Quality adjusted TWiST analysis showed only non-significant differences in duration of good QoL under olaparib (≥65: 8.02 vs. <65: 9.24 months, P=0.48). Conclusions: In this large cohort of BRCA mutated PSOC pts treated with a PARP inhibitor within a phase III trial, no significant differences were detected in terms of efficacy, safety, and QoL with olaparib treatment for pts ≥65 years compared to younger pts. This information supports the use of PARP inhibitors as maintenance therapy for PSOC pts irrespective of age. Clinical trial information: NCT01874353.