Individualized Maintenance Niraparib Dosing Confers Favorable OS in Recurrent Ovarian Cancer

The use of an individualized starting dose (ISD) of niraparib (Zejula) led to a trend toward improved overall survival (OS) as maintenance therapy compared with placebo in Chinese patients with platinum-sensitive, recurrent ovarian cancer regardless of germline BRCA mutation status, according to interim survival data from the phase 3 NORA trial (NCT03705156) that were presented at the 2022 ESMO Virtual Plenary.¹

The median OS in the intention-to-treat (ITT) population was 46.3 months with niraparib vs 43.4 months with placebo (HR, 0.82; 95% CI, 0.56-1.21). The median OS in the germline BRCA-mutant subgroup was not reached with niraparib vs 47.6 months with placebo (HR, 0.76; 95% CI, 0.40-1.46). The median OS in the non–germline BRCA-mutant subgroup was 43.1 months with niraparib vs 38.4 months with placebo (HR, 0.86; 95% CI, 0.53-1.38).

Investigators did not identify any new safety signals with the long-term follow-up. The final prespecified OS analysis of the trial is expected in 2023.

The results were particularly noteworthy because 43% (n = 38/88) of patients in the placebo arm went on to receive at least 1 dose of a PARP inhibitor after progression.

“We are proud to present this new interim OS data analysis from the NORA study for Chinese patients at ESMO, as it adds to the already existing body of evidence from the study to support the clinical profile of ZEJULA 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.

“As one of the most commonly diagnosed gynecologic cancers in China, we are committed to address the urgent need for effective treatment options in ovarian cancer care for patients in China. ZEJULA is well positioned in China as the only PARP inhibitor approved as maintenance monotherapy for patients in both first-line and recurrent settings regardless of biomarker status.”

To be eligible for enrollment in NORA, patients had to be women at least 18 years of age with high-grade serous or dominantly high-grade serous ovarian cancer and have received two lines of platinum-containing chemotherapy.² Complete or partial response to frontline chemotherapy was required, as were 4 cycles of carboplatin, cisplatin, or nedaplatin in the second-line setting.

Investigators randomly assigned 265 patients with platinum-sensitive recurrent ovarian cancer were to niraparib or placebo as maintenance therapy until disease progression.

The study was originally designed to evaluate 300 mg of oral niraparib once daily. After the first 16 patients were treated with the fixed starting dose, the protocol was revised to use an ISD based on the retrospective analysis from the NOVA trial showing improved safety and comparable efficacy with the ISD.

The primary end point was PFS as assessed by blinded independent central review. Secondary end points include chemotherapy-free interval, time to first subsequent anti-cancer therapy, and OS.

The starting dose was individualized at 200 mg except for patients with a baseline body weight of 77 kg or greater and a platelet count of at least 150K/μL, in which case the starting dose was 300 mg.

Topline results released in September 2020 demonstrated that niraparib led to a significant improvement in progression-free survival (PFS) in Chinese patients with platinum-sensitive, recurrent ovarian cancer, regardless of biomarker status (HR, 0.32; 95% CI, 0.23-0.45; P <.0001). The median PFS was 18.3 months (95% CI, 10.9-not evaluable) with niraparib vs 5.4 months (95% CI, 3.7-5.7) with placebo.

The median follow-up time for interim OS analysis in the niraparib and placebo arm was 45.7 and 44.5 months, respectively.

Additional survival results adjusted for subsequent PARP inhibitor therapy showed that the median OS in the ITT population was 46.3 months with niraparib vs 34.3 months with placebo (HR, 0.69; 95% CI, 0.45-1.07). The median OS in the germline BRCA-mutant subgroup was not reached with niraparib vs 42.1 months with placebo (HR, 0.88; 95% CI 0.39-2.01). The median OS in the non–germline BRCA-mutant subgroup was 43.1 months with niraparib vs 32.6 months with placebo (HR, 0.62; 95% CI 0.37-1.05).

References

1. 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 16, 2022. https://bit.ly/3Wsv24p
2. Clinical trial evaluating the efficacy and safety of ZL-2306 (niraparib) in ovarian cancer patient. ClinicalTrials.gov. Updated October 15, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03705156