Greater Progression-Free Survival Benefit of Maintenance Olaparib in BRCA-Mutant Platinum-Sensitive Recurrent Serous Ovarian Cancer


Key Points

  • The progression-free survival benefit of maintenance olaparib was greatest in patients with a BRCA mutation.
  • Second interim analysis showed no overall survival benefit of olaparib among all patients or among those with a BRCA mutation.

A recently reported phase II trial indicated that maintenance therapy with the PARP inhibitor olaparib significantly improved progression-free survival vs placebo in patients with platinum-sensitive serous ovarian cancer. As reported in The Lancet Oncology by Ledermann et al, a preplanned retrospective analysis of outcomes according to BRCA status indicated better progression-free survival outcome in patients with vs without BRCA mutation. A second interim overall survival analysis showed no improvement with olaparib in all patients or in those with BRCA mutation.

Study Details

In the double-blind trial, 265 patients who had received at least two platinum-based regimens and had a partial or complete response to the most recent were randomized to maintenance treatment with olaparib at 400 mg twice daily (n = 136) or placebo (n = 129). Randomization was stratified by time to progression on the penultimate platinum-based regimen, response to the most recent platinum-based regimen, and ethnicity. The primary endpoint was progression-free survival in the overall population and by BRCA status.

BRCA status was known for 131 (96%) patients in the olaparib group and 123 (95%) patients in the placebo group; 74 (56%) and 62 (50%) had deleterious or suspected deleterious germline or tumor BRCA mutations.

Progression-Free Survival

Median progression-free survival was 8.4 months in the olaparib group vs 4.8 months in the placebo group (hazard ratio [HR] = 0.35, P < .0001) among all patients, 11.2 vs 4.3 months (HR = 0.18, P < .0001) among patients with a BRCA mutation, and 7.4 vs 5.5 months (HR = 054, P = .0075) among those with wild-type BRCA.

Overall Survival

At the second interim overall survival analysis (58% maturity), median overall survival was 29.8 months in the olaparib group vs 27.8 months in the placebo group (HR = 0.88, P = .44) among all patients, 34.9 vs 31.9 months (HR = 0.73, P = .19) among those with BRCA mutation, and 24.5 vs 26.2 months (HR =- 0.99, P = .96) among those with wild-type BRCA. At data cutoff for the interim overall survival analysis, 55% of the olaparib group and 84% of the placebo group with a BRCA mutation had received subsequent cancer therapy, with 23% of patients in the placebo group receiving a PARP inhibitor.

Updated Safety Results

The most common grade ≥ 3 adverse events in the olaparib group were fatigue (7% vs 3% in the placebo group) and anemia (5% vs < 1%). Serious adverse events occurred in 18% vs 9%. Adverse events led to dose interruption in 36% vs 16%, dose reduction in 42% vs 22%, and treatment discontinuation in 5% vs 2%. Tolerability of olaparib was similar in patients with mutated BRCA and in the overall population.

The investigators concluded, “These results support the hypothesis that patients with platinum-sensitive recurrent serous ovarian cancer with a BRCA mutation have the greatest likelihood of benefiting from olaparib treatment.”

Jonathan A Ledermann, MD, of University College London, is the corresponding author for The Lancet Oncology article.

The study was funded by AstraZeneca. For full disclosures of the study authors, visit

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