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.
Publication Title
Gynecologic oncology
Document Type
Article
Publication Date
9-1-2026
Keywords
Adult; Aged; Female; Humans; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Ovarian Epithelial; Indazoles; Neoadjuvant Therapy; Neoplasm Staging; Ovarian Neoplasms; Paclitaxel; Piperidines; Poly(ADP-ribose) Polymerase Inhibitors; Taxoids; Advanced ovarian cancer; Neoadjuvant therapy; Niraparib; PARP inhibitor.; washington; swedish
Abstract
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.
Area of Special Interest
Cancer
Area of Special Interest
Women & Children
Specialty/Research Institute
Oncology
Specialty/Research Institute
Obstetrics & Gynecology
Specialty/Research Institute
Pharmacy
DOI
10.1016/j.ygyno.2026.07.023
