Overall survival and updated progression-free survival outcomes in a randomized phase 2 study of combination cediranib and olaparib versus olaparib in relapsed platinum-sensitive ovarian cancer.

Background: Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor and cediranib is an oral anti-angiogenic. In the primary analysis of this phase 2 study, combination cediranib/olaparib improved progression-free survival (PFS) compared to olaparib alone in relapsed platinum-sensitive ovarian cancer. This updated analysis was conducted to characterize overall survival (OS) and update PFS outcomes.

Patients and Methods: 90 patients were enrolled to this randomized, open-label, phase 2 study between October 2011 and June 2013 across nine United States-based academic centers. Data cut-off was December 21, 2016, with a median follow-up of 46 months (mos). Participants had relapsed platinum-sensitive ovarian cancer of high-grade serous or endometrioid histology or had a deleterious germline BRCA1/2 mutation (gBRCAm). Participants were randomized to receive olaparib capsules 400mg twice daily or cediranib 30mg daily and olaparib capsules 200mg twice daily until disease progression.

Results: In this updated analysis, median PFS remained significantly longer with cediranib/olaparib compared to olaparib alone (16.5 vs. 8.2 mos, HR 0.50; p = 0.007). Subset analyses within stratum defined by BRCA status demonstrated statistically significant improvement in PFS (23.7 vs 5.7 mos, p = 0.002) and OS (37.8 vs 23.0 mos, p = 0.047) in gBRCA wild-type/unknown patients, although OS was not statistically different in the overall study population (44.2 vs. 33.3 mos, HR 0.64; p = 0.11). PFS and OS appeared similar between the two arms in gBRCAm patients. The most common grade 3/4 adverse events with cediranib/olaparib remained fatigue, diarrhea, and hypertension.

Conclusions: Combination cediranib/olaparib significantly extends PFS compared to olaparib alone in relapsed platinum-sensitive ovarian cancer. Subset analyses suggest this margin of benefit is driven by PFS prolongation in patients without gBRCAm. OS was also significantly increased by the cediranib/olaparib combination in this subset of patients. Additional studies of this combination are ongoing and should incorporate analyses based upon BRCA status.