Maintenance Therapy With Niraparib Prolongs PFS in Ovarian Cancer

PRIME, a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial, demonstrated the benefit of niraparib as a maintenance therapy for patients with advanced ovarian cancer: © reineg [stock.adobe.com]

Niraparib (Zejula) as a maintenance therapy improved progression-free survival (PFS) in patients with newly diagnosed advanced ovarian cancer after first-line platinum-based chemotherapy, regardless of postoperative residual disease or biomarker status, according to findings from the phase 3 PRIME study (NCT03709316).¹

Among patients treated with niraparib vs placebo, the median PFS was 24.8 vs 8.3 months (HR, 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population.

Safety findings showed that similar proportions of patients between arms (6.7% vs 5.4% for niraparib vs placebo) discontinued treatment due to treatment-emergent adverse events (TEAEs), and 139 (54.5%) patients treated with niraparib had a grade 3 or higher TEAE vs 23 placebo-treated patients (17.8%).

“Our hope is that as real-world evidence emerges, we can provide better confidence to the safety of using a therapy like this. For me, this could be a large cohort of patients that did not receive a PARP inhibitor in the frontline setting,” Robert Coleman, MD, FACOG, FACS, gynecologic oncologist with Texas Oncology, a practice in The US Oncology Network, and Co-Director of the Gynecologic Oncology Group (GOG) Partners Foundation, told Targeted Oncology^TM.

PRIME was a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial which enrolled 384 in Chinese patients with newly diagnosed advanced ovarian cancer after receiving first-line platinum-based chemotherapy. This included patients who underwent R0 resection at primary debulking surgery.^1,2

Enrollment in the study was open to patients aged 18 years or older with a diagnosis of histologically confirmed, high-grade serous or endometrioid epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma, which was FIGO stage III/IV. Patients were eligible for enrollment if they had received primary or interval debulking surgery, regardless of cytoreductive surgery outcome, receipt of primary or interval cytoreductive surgery, and a complete response (CR) or partial response (PR) to first-line platinum-based therapy.³

The study randomized patients in a 2:1 fashion to receive either niraparib or matched placebo for 36 months or until disease progression or unacceptable toxicity.

The primary end point of the study was blinded independent central review-assessed PFS in the intention-to-treat population, and secondary end points were overall survival (OS) and time to first subsequent anti-cancer therapy in the ITT population, PFS and OS in the homologous recombination deficiency subgroup, and safety.

Among those enrolled, patient demographic and baseline characteristics were well balanced between treatment groups, The median age of the 384 randomized patients was 54 years (range, 32-77 years). A total of 108 (28.1%) patients had stage IV disease, 180 (46.9%) received neoadjuvant chemotherapy, 50 (13.0%) achieved suboptimal debulking, and 69 (18.0%) had a partial response to platinum-based chemotherapy.1 Additionally, 125 patients (32.6%) had germline BRCA variants, and homologous recombination status was deficient in 257 patients (66.9%), proficient in 85 (22.1%), and indeterminate in 42 (10.9%).

At the data cutoff date of September 30, 2021, the median follow-up for PFS was 27.5 (IQR, 24.7-30.4) months. These follow-up rates were 27.5 months (95% CI, 25.3-27.6) in the niraparib group and 27.6 months (95% CI, 24.9-30.3) in the placebo group.

Additional findings showed that the median PFS was not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) in patients with germline BRCA variants, and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients without germline BRCA variants, respectively. PFS was not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) in patients who were homologous recombination deficient, and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in patients who were homologous recombination proficient, respectively. Additionally, PFS was 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in patients with optimal and suboptimal debulking, respectively.

A total of 209 patients, including 123 treated with niraparib (58.9%), and 86 treated with placebo (41.4%) had disease progression or died.

For safety, the most common grade 3 or higher TEAEs among patients given niraparib were anemia (18.0%), neutrophil count decreased (17.3%), platelet count decreased (14.1%), and white blood cell count decreased (6.7%). Forty-eight (18.8%) patients in the niraparib group had serious TEAEs vs 11 (8.5%) placebo-treated patients. Further, one patient each in the niraparib group had a case of acute myeloid leukemia and myelodysplastic syndrome, and the patient with acute myeloid leukemia died as a result of this TEAE.

In the niraparib-treated and placebo-treated groups, dose reductions due to TEAEs occurred in 103 (40.4%) and 8 (6.2%) patients, respectively, with the most common TEAEs leading to dose reductions being hematologic TEAEs, including platelet count decreased (24.3%), anemia (10.2%), neutrophil count decreased (9.8%), and white blood cell count decreased (3.1%), in the niraparib group.

REFERENCES:

1. Li N, Zhu J, Yin R, et al. Treatment with niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer: A phase 3 randomized clinical trial. JAMA Oncol. Published July 13, 2023. doi:10.1001/jamaoncol.2023.2283

2. Kong B, Wu L, Zhu J, et al. Efficacy and safety of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer who had measurable residual disease: A post-hoc subgroup analysis of the PRIME study. J Clin Oncol. 2023;41(16):5562. doi:10.1200/JCO.2023.41.16_suppl.5562

3. A study of ZL-2306 (niraparib) as maintenance treatment following first-line chemotherapy in patients with advanced ovarian cancer. ClinicalTrials.gov. Updated June 2, 2021. Accessed July 26, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03709316