Results from a previous study indicated that treatment with the combination would lead to improvement in progression-free survival (PFS) compared with treatment with olaparib alone.
In an open-label phase 3 study of patients with recurrent platinum-sensitive ovarian cancer, PFS was not improved with an all-oral nonplatinum-based chemotherapy regimen compared with platinum-based chemotherapy. In a 3-arm clinical trial, median PFS was 10.3 months in patients randomized to standard of care (either carboplatin/paclitaxel, carboplatin/gemcitabine, or carboplatin/liposomal doxorubicin) versus a median of 10.4 months for the combination of cediranib and olaparib (hazard ratio [HR] vs chemotherapy, 0.856; 95% confidence interval [CI], 0.663-1.105) and a median of 8.2 months in the olaparib monotherapy arm (HR vs chemotherapy, 1.20; 95% CI, 0.933-1.54). These results were reported by Joyce F. Liu, MD, Director of Clinical Research, Gynecologic Oncology, Dana-Farber Cancer Institute, Boston, MA, during this year’s virtual scientific program of the American Society of Clinical Oncology. According to Dr Liu, alternatives to multiple courses of platinum-based therapy would be attractive because repeated platinum therapy can increase the risk of carboplatin allergy and exacerbate neuropathy (paclitaxel) and offer the potential for cumulative hematologic toxicity, said Dr Liu.
Cediranib plus olaparib was thought to have synergistic activity as observed in a preclinical study and ovarian cancer-cell lines. In patients with relapsed platinum-sensitive high-grade ovarian cancer, the combination showed a nearly doubling of median PFS with the combination compared with olaparib alone based on phase 2 study results.
A total of 565 patients were enrolled in the current study. Patients with recurrent platinum-sensitive ovarian cancer were randomized 1:1:1 to standard-of-care platinum-based doublet, olaparib (300 mg twice daily), or the combination of cediranib (30 mg daily) and olaparib (200 mg twice daily). Patients were allowed 1 previous nonplatinum therapy, and there was no limit on previous platinum therapies. There were >90% of patients with high-grade serous histology and nearly 25% with a deleterious germline BRCA mutation.
Among 460 patients evaluable for response, objective response rates (ORRs) were 71.3%, 69.4%, and 52.4% in the chemotherapy, cediranib plus olaparib, and olaparib-alone arms, respectively. Prespecified subset analyses were conducted for outcomes in patients with germline BRCA mutations and BRCA wild-type mutations. Median PFS rates were 10.5, 12.7, and 18.0 months in the chemotherapy, olaparib monotherapy, and combined cediranib/olaparib arms, respectively, among patients with germline BRCA mutations; ORRs were 71%, 90%, and 89%, respectively, in this subset.
Among patients with germline BRCA wild-type, median PFS rates were 9.7, 6.6, and 8.9 months in the chemotherapy, olaparib monotherapy, and cediranib plus olaparib arms, respectively; ORRs were 72%, 40%, and 64%, respectively. Among the 3 treatment arms at the time of the analysis, no difference was observed in overall survival. In the chemotherapy arm, 53 patients initiated nonprotocol therapy before progression, most of whom received a maintenance poly (ADP-ribose) polymerase inhibitor. Median PFS was consistent with the primary PFS analysis when censoring for noncompliance events in the control arm, according to Dr Liu.
Source: Liu JF, et al. J Clin Oncol. 2020;38(15_suppl). Abstract 6003.