Cediranib Plus Olaparib in Relapsed Platinum-Sensitive Ovarian Cancer
Posted: Monday, March 18, 2019
The updated results of a randomized phase II trial, conducted by Joyce F. Liu, MD, PhD, of the Dana-Farber Cancer Institute, Boston, confirmed that progression-free survival was significantly longer with the combination of the antiangiogenic tyrosine kinase inhibitor cediranib and the PARP inhibitor olaparib compared with olaparib alone in women with relapsed platinum-sensitive ovarian cancer. The updated data also revealed that overall survival was significantly better with the combination therapy in a subset of patients. The study findings were published in the Annals of Oncology.
Between 2011 and 2013, 90 women with relapsed platinum-sensitive ovarian cancer of high-grade serous or endometrioid histology or with a deleterious germline BRCA1/2 mutation were the focus of the study. They were randomly assigned to receive cediranib at 30 mg daily and olaparib capsules at 200 mg twice daily or olaparib capsules at 400 mg twice daily until disease progression.
The median progression-free survival remained significantly longer with cediranib plus olaparib compared with olaparib alone at 16.5 months versus 8.2 months, respectively; overall survival was not statistically different in the overall study population. However, in a subset analysis, women with germline BRCA wild-type/unknown had significantly improved progression-free and overall survival with the combination therapy compared with olaparib alone. However, this response was not observed in women with a germline BRCA1/2 mutation.
As for toxicity, updated safety data confirmed that drug-related adverse events were more common in the combination arm than in the olaparib alone. The grade 3 or 4 adverse events associated with cediranib plus olaparib included fatigue, diarrhea, and hypertension.
“The findings of a differential effect of cediranib plus olaparib in BRCA-mutated versus BRCA wild-type patients might suggest further stratification of the therapeutic approach to patient treatment,” concluded coauthor Ursula A. Matulonis, MD, of Harvard Medical School, and colleagues.
Disclosure: The study authors’ disclosure information may be found at academic.oup.com.