Randomised phase II trial of olaparib compared to weekly paclitaxel or olaparib plus cediranib in patients with platinum-resistant ovarian cancer (OCTOVA)

Abstract

Background The main aims of the OCTOVA trial were to compare the efficacy and toxicity of olaparib (O) with weekly paclitaxel (wP) and also the oral combination of olaparib plus cediranib (O+C) in recurrent ovarian cancer (OC). Methods Participants with high grade ovarian, fallopian tube, primary peritoneal cancer who relapsed within 12 months of previous platinum-based therapy were randomised, with stratification for germline BRCA1/2 mutation status, prior PARP inhibitor (PARPi) or anti-angiogenic therapy, to receive O (300mg daily) or either wP (80mg/m2 d1,8,15, q28) or O+C (300mg/20mg daily respectively). Treatment continued until disease progression or unacceptable toxicity. Primary endpoint was Progression Free Survival (PFS). Secondary endpoints were safety and tolerability of the combination of O+C, overall survival, objective response rate, and quality of life. A sample size of 138 (46 per arm) was sufficient to observe HR 0.64 in favour of O+C compared to O alone and 1.44 for wP compared to O (20% one-sided type I error, 80% power, 15% dropout, one-sided p-value <0.2). Results OCTOVA recruited 139 participants, median 65 years (IQR:38-84), from 15 UK centres over 34 months. 31 (22%) had had prior PARPi therapy, 47 (34%) prior anti-angiogenic therapy. 41 (29%) had known germline BRCA1/2 mutations. 125 (90%) had relapsed <6 months after prior platinum. Median 2 prior lines of chemotherapy (range 1-7). There was no difference in PFS between wP and O (HR=0.97, 60%CI: 0.79, 1.19; p=0.55). PFS was increased for O+C compared to O (HR=0.70; 60%CI: 0.57, 0.86; p=0.08). There were 239, 176, and 137 treatment related adverse events (all grades) in the O+C, wP and O arms respectively. Conclusions The OCTOVA trial demonstrated that the combination of O+C showed greater efficacy than O alone, but we did not find evidence that wP was inferior to O in women with multiply relapsed OC.