Background

Post-hoc analysis of NOVA study suggested that patients with low body weight (< 77 kg) or low platelet count (< 150,000/μL) may benefit from an initial starting dose of niraparib 200 mg without compromising efficacy. We aimed to prospectively assess the efficacy and safety of niraparib with an individualized starting dose (ISD) in Chinese patients.

Methods

NORA trial was conducted in 32 hospitals in China. Eligible patients were women with PSROC who had either germline BRCA mutation or high-grade serious histologic features and who had a complete or partial response after completion of the last round of platinum therapy. Patients were randomly allocated (2:1) to receive oral niraparib or placebo once daily. The starting dose was individualized (ISD) per baseline body weight and platelet count (200 mg for patients with baseline body weight < 77 kg or platelet count < 150,000/μL; otherwise, 300 mg). The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.

Results

From September 26 2017 to February 2 2019, 265 patients were randomized to niraparib (n=177) or placebo (n=88); 16 patients received fixed starting dose of 300 mg and 249 patients received an ISD (300 mg, n=14; 200 mg, n=235) under the amended protocol. The median PFS was significantly longer for patients on niraparib versus placebo; 18.3 (95% CI, 10.9, not evaluable) versus 5.4 (95% CI, 3.7, 5.7) months (HR=0.32; 95% CI, 0.23–0.45; p <0.0001). Grade ≥3 treatment emergent adverse events (TEAE) occurred in 50.8% and 19.3% of patients (niraparib vs placebo), especially for hematological TEAE reported in the Table. Table: LBA29

Hematology TEAE of Grade ≥ 3

Conclusions

This is the first study to demonstrate the efficacy and safety of niraparib in Chinese patients with PSROC. ISD of niraparib is effective and safe and should be considered a standard clinical practice in this patient population.

Clinical trial identification

NCT03705156.

Legal entity responsible for the study

Zai Lab (Shanghai) Co., Ltd.

Funding

Zai Lab (Shanghai) Co., Ltd., Shanghai, China. National Major Scientific and Technological Special Project for “Significant New Drugs Development” in 2018 (No. 2018ZX09736019), China.

Disclosure

All authors have declared no conflicts of interest.