Comparing niraparib versus platinum-taxane doublet chemotherapy as neoadjuvant treatment in patients with newly diagnosed homologous recombination-deficient stage III/IV ovarian cancer: Findings from cohort C of the OPAL phase 2 trial.

BACKGROUND: Despite therapeutic improvements in advanced ovarian cancer (aOC), prognosis remains poor for patients with residual disease after cytoreductive surgery. Reported here are results from cohort C of the phase 1b/2 OPAL study of a neoadjuvant poly(ADP-ribose) polymerase (PARP) inhibitor for aOC. METHODS: Eligible adults with newly diagnosed stage III/IV homologous recombination-deficient (HRd) aOC and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 were randomized 1:1 to receive neoadjuvant platinum-taxane chemotherapy (platinum-taxane) or niraparib. During the prescreening period, patients received 1 run-in cycle of carboplatin-paclitaxel. After neoadjuvant therapy, patients with an unconfirmed complete/partial response (CR/PR) or stable disease per RECIST could undergo interval debulking surgery (IDS), followed by adjuvant platinum-taxane-based chemotherapy. After adjuvant therapy, patients without progression received niraparib-based maintenance treatment. Primary endpoint was pre-IDS unconfirmed investigator-assessed overall response rate (ORR) per RECIST. Secondary endpoints included safety. RESULTS: Of 36 patients randomized, 19 received niraparib and 17, platinum-taxane. Baseline demographics and characteristics were similar between arms. Overall, the pre-IDS unconfirmed ORR was 31.6% (CR/PR, 0/31.6%) with niraparib and 70.6% (CR/PR, 0/70.6%) with platinum-taxane. The pre-IDS unconfirmed ORR (80% CI) difference was -39.0% (-56.8% to -17.7%), favoring platinum-taxane. The trial was closed early for futility. Grade ≥3 adverse-event rates during the neoadjuvant period were 42% and 59% in the niraparib and platinum-taxane arms, respectively. No fatal serious adverse events occurred. CONCLUSIONS: In newly diagnosed HRd aOC, neoadjuvant niraparib did not improve ORR versus standard platinum-based chemotherapy, and the trial was discontinued. The safety profile was consistent with those of previous PARP inhibitor studies.