Niraparib Maintenance Demonstrates Favorable OS Trend in Platinum-Sensitive Recurrent Ovarian Cancer

Treatment with niraparib (Zejula) in the maintenance setting demonstrated a favorable trend towards improved overall survival (OS) compared with placebo in patients with platinum-sensitive recurrent ovarian cancer regardless of the presence of BRCA mutations, according to interim data from the phase 3 NORA study (NCT03705156).¹

With a median follow-up time of 45.7 and 44.5 months in the niraparib and placebo cohorts, respectively, the median OS in the intent-to-treat (ITT) population was 46.32 months vs 43.37 months in each cohort (HR, 0.821; 95% CI, 0.558-1.207). Adjusting for patients who received subsequent PARP inhibitor therapy, the median OS in the ITT population was 46.3 months vs 34.3 months in the niraparib and placebo cohorts, respectively (HR, 0.69; 95% CI, 0.45-1.07).

Additionally, the median OS in the BRCA mutation subgroup was not reached (95% CI, 35.38-not evaluable [NE]) vs 47.61 months (95% CI, 31.57-NE) in each respective cohort in the unadjusted OS analysis (HR, 0.77; 95% CI, 0.40-1.47). Following adjustments, the median OS was not reached (95% CI, 35.38-NE) and 42.09 (95% CI, 33.08-NE), respectively (HR, 0.39-2.03).

Moreover, the median OS in the non-gBRCA mutation subgroup was 43.1 months (95% CI, 38.41-NE) vs 38.41 months (95% CI, 29.54-NE) in each respective arm in the unadjusted analysis (HR, 0.855; 95% CI, 0.529-1.381). After adjustments were made, the median OS was 43.10 vs 32.59, respectively (HR, 0.62; 95% CI, 0.37-1.05).

“We are proud to present this new interim OS data analysis from the NORA study for Chinese patients at the 2022 European Society for Medical Oncology (ESMO) Congress Virtual Plenary, as it adds to the already existing body of evidence from the study to support the clinical profile of [niraparib] as a second-line maintenance therapy for ovarian cancer regardless of biomarker status,” Josh Smiley, chief operating officer of Zai Lab, said in a press release.²

Investigators of the phase 3 NORA study randomly assigned 265 patients with platinum-sensitive recurrent ovarian cancer 2:1 to receive either maintenance niraparib or placebo until disease progression. The starting dose for niraparib was individualized at 200 mg for patients with a body weight of less than 77 kg or a platelet count of less than 150,000/μL at baseline, whereas patients with a baseline body weight of 77 kg or more and a platelet count of at least 150,000/μL received a starting dose of 300 mg.

The primary end point of the NORA study was progression-free survival (PFS) as assessed by blinded independent central review. Key secondary end points included chemotherapy-free interval, the time to first subsequent anti-cancer treatment, and OS.

Patients 18 years and older with high-grade serous or dominantly high-grade serous ovarian cancer were eligible to enroll on the study. Additional inclusion criteria included having achieved a complete or partial response to first-line platinum-based chemotherapy, receiving at least 4 cycles of second-line platinum-containing chemotherapy, and having an ECOG performance status of 0 or 1. Patients with symptomatic brain metastases or leptomeningeal metastases that have not been controlled were not eligible for enrollment.

PFS findings from the NORA study were previously read out in September 2020. The median PFS was 18.3 months (95% CI, 10.9-NE) for patients receiving niraparib vs 5.4 months (95% CI, 3.7-5.7) for those receiving placebo.

Results from the NORA trial indicated no new safety signals for niraparib based on long-term follow-up.

Reference

1. Mirza MR, Wu X, Zhu J, et al. An ad hoc interim overall survival results of niraparib with individualized starting dose as maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer (NORA): A double-blind, randomized, placebo-controlled, phase III trial. Ann Oncol. Published online December 15, 2022. doi:10.1016/j.annonc.2022.11.007
2. Zai Lab presents interim overall survival data for ZEJULA® (niraparib) from the NORA phase 3 study at the ESMO Virtual Plenary. News release. Zai Lab Limited. December 15, 2022. Accessed December 21, 2022. bit.ly/3VkleZ0