No Difference in PFS Between Platinum-Based Chemotherapy and Olaparib in Women with Platinum-Sensitive Ovarian Cancer

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An all-oral nonplatinum-based chemotherapy regimen did not improve progression-free survival (PFS) compared with platinum-based chemotherapy in an open-label phase 3 study of patients with recurrent platinum-sensitive ovarian cancer.

Median PFS in a 3-arm clinical trial 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 (Recentin) and olaparib (Lynparza; 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), reported Joyce F. Liu, MD, Director of Clinical Research, Gynecologic Oncology, Dana-Farber Cancer Institute, Boston, MA, during the 2020 virtual scientific program of the American Society of Clinical Oncology.

Alternatives to multiple courses of platinum-based therapy would be attractive since repeated platinum therapy can increase the risk for carboplatin allergy and exacerbate neuropathy (paclitaxel) and have 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. Results of the combination from a phase 2 study showed a nearly doubling of median PFS with the combination compared with olaparib alone in patients with relapsed platinum-sensitive high-grade ovarian cancer.

The current study enrolled 565 patients with recurrent platinum-sensitive ovarian cancer, who were randomized 1:1:1 to standard-of-care platinum-based doublet, olaparib (300 mg twice daily), or the combination of cediranib (30 mg a day) and olaparib (200 mg twice daily). Patients were allowed one previous nonplatinum therapy and no limit on previous platinum therapies.

More than 90% of patients had high-grade serous histology and nearly 25% had a deleterious germline BRCA mutation.

Among 460 patients evaluable for response, objective response rates (ORRs) were 71.3% in the chemotherapy arm, 69.4% in the cediranib plus olaparib arm, and 52.4% in the olaparib-alone arm.

Prespecified subset analyses were conducted for outcomes in patients with germline BRCA mutations and BRCA wild-type.

Among patients with germline BRCA mutations, median PFS was 10.5 months in the chemotherapy arm, 12.7 months in the olaparib monotherapy arm, and 18.0 months in the combined cediranib/olaparib arm. The ORRs in this subset were 71%, 90%, and 89%, respectively.

Among patients with germline BRCA wild-type, median PFS was 9.7 months in the chemotherapy arm, 6.6 months in the olaparib monotherapy arm, and 8.9 months in the cediranib plus olaparib arm, with ORRs of 72%, 40%, and 64%, respectively.

At the time of the analysis, no difference in overall survival was observed among the 3 treatment arms.

Fifty-three patients in the chemotherapy arm initiated nonprotocol therapy prior to progression, most of whom received a maintenance poly (ADP-ribose) polymerase inhibitor. When censoring for noncompliance events in the control arm, median PFS was consistent with the primary PFS analysis, said Dr Liu.

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