CHICAGO—The combination of the investigational oral agents cediranib plus olaparib “significantly extended” progression-free survival (PFS) and objective response rate versus olaparib alone in women with platinum-sensitive ovarian cancer or ovarian cancer related to mutations in BRCA genes, the first study to explore this combination concluded at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
“The significant activity that we saw with the combination suggests that this could potentially be an effective alternative to standard chemotherapy,” said Joyce Liu, MD, MPH, an instructor in medical oncology at Dana-Farber Cancer Institute in Boston, MA. “At the same time, this approach is not yet ready for clinical practice, as neither of these drugs is currently [Food and Drug Administration]–approved for ovarian or any other cancer. We also need additional clinical trials to confirm the findings of this study to see how this combination compares to standard treatment.”
Median PFS, the primary study endpoint, was 17.7 months with cediranib plus olaparib (19 PFS events) versus 9 months with olaparib alone (28 PFS events; hazard ratio [HR], 0.42; 95% CI: 0.23-0.75, P = 0.005).
Preclinical studies have suggested that combining PARP inhibitors and antiangiogenics is synergistic, and a phase 1 study of olaparib and cediranib demonstrated activity in patients with ovarian cancer and triple negative breast cancer, reported Dr. Liu.
In this phase 2 open-label study, patients with recurrent platinum-sensitive, high-grade serous or BRCA-related ovarian cancer were randomly assigned across nine centers to olaparib 400 mg capsules twice daily (n=46) or olaparib 200 mg capsules twice daily plus cediranib 30 mg/day (n=44). Patients were stratified by BRCA status and prior antiangiogenic therapy. “No prior antiangiogenics in the recurrent setting or prior PARP inhibitor was allowed,” she said.
Patients randomly assigned to cediranib plus olaparib were required to have their blood pressure taken twice daily.
Of the patients, 47 were known BRCA carriers—24 in the olaparib arm and 23 in the cediranib plus olaparib arm.
“At a planned interim analysis, the Data Safety Monitoring Board recommended release of data,” Dr. Liu said.