Abstract
BACKGROUND: Olaparib (AZD2281) is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor that has shown antitumor activity in patients with high-grade serous ovarian cancer with or without BRCA1 or BRCA2 germline mutations. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2 study to evaluate maintenance treatment with olaparib in patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer who had received two or more platinumbased regimens and had had a partial or complete response to their most recent platinum-based regimen. Patients were randomly assigned to receive olaparib, at a dose of 400 mg twice daily, or placebo. The primary end point was progression-free survival according to the Response Evaluation Criteria in Solid Tumors guidelines. RESULTS: Of 265 patients who underwent randomization, 136 were assigned to the olaparib group and 129 to the placebo group. Progression-free survival was significantly longer with olaparib than with placebo (median, 8.4 months vs. 4.8 months from randomization on completion of chemotherapy; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.25 to 0.49; P<0.001). Subgroup analyses of progression-free survival showed that, regardless of subgroup, patients in the olaparib group had a lower risk of progression. Adverse events more commonly reported in the olaparib group than in the placebo group (by more than 10% of patients) were nausea (68% vs. 35%), fatigue (49% vs. 38%), vomiting (32% vs. 14%), and anemia (17% vs. 5%); the majority of adverse events were grade 1 or 2. An interim analysis of overall survival (38% maturity, meaning that 38% of the patients had died) showed no significant difference between groups (hazard ratio with olaparib, 0.94; 95% CI, 0.63 to 1.39; P = 0.75). CONCLUSIONS: Olaparib as maintenance treatment significantly improved progression-free survival among patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer. Interim analysis showed no overall survival benefit. The toxicity profile of olaparib in this population was consistent with that in previous studies. (Funded by Astra- Zeneca; ClinicalTrials.gov number, NCT00753545.).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1382-1392 |
| Number of pages | 11 |
| Journal | New England Journal of Medicine |
| Volume | 366 |
| Issue number | 15 |
| DOIs | |
| State | Published - Apr 12 2012 |
Funding
This work was part funded by EPSRC, and the International Collaborative Energy Technology R&D Program of the Korean Institute of Energy Technology Evaluation and Planning (KETEP) with financial resource from the Ministry of Trade, Industry & Energy, Republic of Korea (no. 20148520011250). J. T.-W. W. acknowledges Swire Educational Trust for supporting his DPhil study at Oxford, and thanks Will Y.-K. Peng, and the members in the HJS and RJN group for helpful discussion. W. Z. thanks the Supergen super solar project for funding support. R. Z. thanks Prof. Bing Shen, Mr Haoran Ma and Xianguo Lang from the School of Earth and Space Sciences at Peking University for help in the ICP-OES analysis.
ASJC Scopus subject areas
- General Medicine
