In the SOLO1 clinical trial, maintenance olaparib resulted in a significant improvement in progression-free survival (PFS) for patients with newly diagnosed, BRCA1- and/or BRCA2-mutated, advanced ovarian cancer compared with placebo (hazard ratio [HR] = 0.30; 95% confidence interval [CI], 0.23-0.41), the results of which were published in 2018 in The New England Journal of Medicine.
In a randomized, double-blind, placebo-controlled, multicenter, phase III trial presented at the 2019 ASCO Annual Meeting, researchers further investigated the SOLO1 cohort to determine PFS for subgroups of patients with BRCA1 or BRCA2 mutations. They observed a significant PFS benefit with olaparib regardless of BRCA mutation status.
All patients (n=391) were in clinical complete or partial response to platinum-based chemotherapy and were randomized to receive maintenance olaparib 300 mg twice daily or placebo. After two years, patients with no evidence of disease discontinued treatment, but patients with evidence of disease could continue. Of this cohort, 282 had BRCA1 mutation (72%), 106 had BRCA2 mutation (27%), and three had both mutations (1%).
Two patients in the olaparib cohort had somatic BRCA mutation, while the rest had germline BRCA mutation. At the primary data cutoff, 155 patients in the BRCA1-mutated group (55%), 43 in the BRCA2-mutated group (41%), and none in the BRCA1/2-mutated group experienced disease progression. Median PFS (primary outcome) in the BRCA1 mutation cohort was 41.4 months with olaparib and 13.8 months with placebo (HR=0.41; 95% CI, 0.30-0.56). Median PFS in the BRCA2 mutation cohort was not reached with olaparib and 13.8 months with placebo (HR=0.20; 95% CI, 0.10-0.37).
The percentage of BRCA1-mutated patients who received olaparib and were progression-free at one, two, and three years was 86%, 69%, and 53% compared with 52%, 36%, and 26%, respectively, among those receiving placebo. The percentage of BRCA2-mutated patients who received olaparib and were progression-free at these timepoints was 92%, 85%, and 80%, respectively, compared with 50%, 32%, and 29%, respectively, among those receiving placebo.
“Statistical tests were not used to compare BRCA1- and BRCA2-mutated patients, but those with BRCA2 mutation appeared to receive greater benefit from maintenance olaparib than those with BRCA1 mutation,” the researchers added.
Friedlander M, Moore KN, Colombo N, et al. Efficacy of maintenance olaparib for newly diagnosed, advanced ovarian cancer patients (pts) by BRCA1 or BRCA2 mutation in the phase III SOLO1 trial. Abstract #5551. Presented at the 2019 ASCO Annual Meeting, Chicago, IL, June 1, 2019.