Greater Progression-Free Survival Benefit of Maintenance Olaparib in BRCA-Mutant Platinum-Sensitive Recurrent Serous Ovarian Cancer
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 www.thelancet.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
