Maintenance olaparib (Lynparza) appeared to be associated with an overall survival benefit vs placebo in women with platinum-sensitive serous ovarian cancer and BRCA1 and BRCA2 mutations, according to an updated analysis of a phase II trial reported in The Lancet Oncology by Jonathan A. Ledermann, MD, of the Cancer Research UK and University College London Cancer Trials Centre, and colleagues. Maintenance olaparib was previously reported to significantly prolong progression-free survival in the study.
In the double-blind trial, 265 patients from 82 sites in 6 countries who had platinum-sensitive recurrent serous ovarian cancer and had received two or more courses of platinum-based chemotherapy and had responded to their latest regimen were randomized to receive oral maintenance olaparib at 400 mg twice daily (n = 136) or placebo (n = 129). The primary endpoint was progression-free survival; the current analysis of overall survival, a secondary endpoint, is from the third data analysis after more than 5 years of follow-up in the intent-to-treat population. The study was not statistically powered to assess overall survival; thus, the analysis is descriptive, and the P values are nominal.
Survival Outcomes and Toxicity
The hazard ratio (HR) for overall survival for maintenance olaparib vs placebo among all patients was 0.73 (nominal P = .025, not meeting the required threshold for statistical significance of < .0095). Median overall survival was 29.8 months vs 27.8 months. Among the 136 patients with BRCA1 or BRCA2 mutations, median overall survival was 34.9 vs 30.2 months (HR = 0.62, nominal P = .025). Among those with wild-type BRCA, median overall survival was 24.5 vs 26.6 months (HR = 0.83, nominal P = .37). Overall, 11 of 74 patients (15%) with BRCA mutations in the olaparib group received maintenance olaparib for at least 5 years.
Common grade ≥ 3 adverse events in the olaparib and placebo groups were fatigue (8% vs 3%) and anemia (6% vs1%). Serious adverse events occurred in 22% vs 9%. Among 32 patients receiving olaparib for at least 2 years, adverse events included low-grade nausea (75%), fatigue (56%), vomiting (38%), and anemia (25%).
The investigators concluded: “Despite not reaching statistical significance, patients with BRCA-mutated platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy after platinum-based chemotherapy appeared to have longer overall survival, supporting the reported progression-free survival benefit. Clinically useful long-term exposure to olaparib was seen with no new safety signals. Taken together, these data support both the long-term clinical benefit and tolerability of maintenance olaparib in patients with BRCA-mutated platinum-sensitive recurrent serous ovarian cancer.”
The study was funded by AstraZeneca.