Multicenter phase 2 trial of neoadjuvant niraparib monotherapy for unresectable, HRD-positive, high-grade serous ovarian cancer

Neoadjuvant chemotherapy followed by interval debulking surgery is standard treatment for advanced ovarian cancer that is unlikely to achieve optimal cytoreduction. The phase 2 NANT trial, at six centers in China, evaluated a chemotherapy-free regimen of neoadjuvant niraparib monotherapy in HRD-positive disease initially unsuitable for primary debulking surgery. Eligible patients were aged 18-75 years, had treatment-naïve, FIGO stage III-IV HRD-positive high-grade ovarian cancer, an ECOG performance status of 0-2, with a low likelihood of complete primary debulking surgery based on prespecified criteria. Patients received oral niraparib for two 28-day cycles. Protocol-permitted supportive care was provided as clinically indicated. Co-primary endpoints were investigator-assessed objective response rate (ORR) and R0 resection rate after interval debulking surgery. A total of 67 patients were enrolled (all female; all identified as Han Chinese; median age 55 years; IQR 50-62). At the data cutoff, median follow-up was 37.7 months (IQR 31.8-48.5). Among 48 response-evaluable patients, 30 achieved an objective response (ORR 63%; 95% CI 47-76). Among 40 operated patients, 32 achieved R0 resection (80%; 95% CI 64-91). The most common grade 3-4 treatment-related adverse events were thrombocytopenia (48% of patients), leukopenia (19%), anemia (18%), and neutropenia (13%). Serious adverse events occurred in 28%; no treatment-related deaths occurred.The authors conclude that neoadjuvant niraparib showed antitumor activity and enabled R0 resection in selected patients with HRD-positive advanced ovarian cancer who were initially unsuitable for primary debulking surgery.