5003 Background: Olaparib (AZD2281) is an oral PARP inhibitor that has shown antitumor activity in patients (pts) with high-grade serous ovarian cancer (SOC) with and without BRCA1 or BRCA2 mutations. This randomized, double-blind, multicenter, placebo-controlled Phase II study evaluated maintenance treatment with olaparib in pts with high-grade PSR SOC (clinicaltrials.gov; NCT00753545 ).
METHODS
Pts with PSR SOC who had received ≥2 previous platinum regimens and were in a maintained partial or complete response following their last platinum-containing regimen were randomized to oral olaparib 400 mg bid or placebo. The primary endpoint was progression-free survival (PFS) by RECIST. Secondary endpoints included time to progression (TTP) by CA-125 (GCIG criteria) or RECIST, overall survival (OS) and safety.
RESULTS
265 pts were randomized (136 to olaparib and 129 to placebo). Demographics and baseline characteristics were generally well balanced. At data cut-off there were 153 (58%) progression events. PFS by RECIST was significantly longer in the olaparib than the placebo group (HR, 0.35; 95% CI 0.25-0.49; P<0.00001; median 8.4 vs 4.8 months). TTP by CA-125 or RECIST was also significantly longer in the olaparib than the placebo group (HR, 0.35; 95% CI 0.25-0.47; P<0.00001; median 8.3 vs 3.7 months). At data cut-off OS data were too immature for analysis. 68 (50%) and 21 (16%) remain on olaparib or placebo, respectively. AEs more commonly reported on olaparib than placebo (by >10%) were nausea (68% vs 35%), fatigue (49% vs 38%), vomiting (32% vs 14%) and anemia (17% vs 5%); the majority of AEs were CTCAE grade 1 or 2. The most frequently reported CTCAE grade ≥3 events were fatigue (9 pts) and anemia (7 pts) for olaparib, and abdominal pain and fatigue (4 pts each) for placebo. 3 (2.2%) pts on olaparib and 1 (0.8%) on placebo had AEs that led to treatment discontinuation. 31 pts (23%) in the olaparib group and 9 (7%) in the placebo group had both dose reductions and interruptions.
CONCLUSIONS
In pts with PSR SOC, maintenance treatment with olaparib 400 mg bid provided a significant improvement in PFS. Olaparib was well tolerated, and toxicities were consistent with previous studies.