Niraparib Maintenance Therapy Improves PFS by 55% in Advanced Ovarian Cancer

Niraparib maintenance therapy was shown to effectively extend progression-free survival (PFS) among individuals with recently diagnosed advanced ovarian cancer (aOC), regardless of their residual disease or biomarker status following surgery.

“The phase 3 PRIMA study demonstrated that niraparib, a potent, highly selective PARP inhibitor, significantly prolonged PFS vs placebo in the first-line maintenance setting regardless of HRD status,” the authors noted, referencing the 2019 PRIMA study. “However, PRIMA mainly enrolled patients at a very high risk of disease progression and excluded patients with stage III disease who had undergone R0 resection at primary debulking surgery and used an individualized starting dose (ISD) based on baseline body weight and platelet count, a strategy to improve the safety profile of niraparib, in around 35% of patients only.”

The new phase 3 PRIME study, which was published in JAMA Oncology, utilized an ISD and demonstrated significant improvements in PFS across a broad patient population, even in those without postoperative residual disease. According to the study authors, these findings suggest that the use of niraparib in the first-line maintenance context is both safe and beneficial.

The multicenter, randomized, double-blind, placebo-controlled, phase 3 trial enrolled 384 patients with newly diagnosed aOC across 29 hospitals in China. Participants underwent primary or interval debulking surgery and received first-line platinum-based chemotherapy. By the data cutoff date in September 2021, the median follow-up for PFS was 27.5 months.

Patients were randomly assigned 2:1 to receive either niraparib or placebo with an ISD, which was tailored based on individual characteristics. Those with a body weight of less than 77 kg and/or a platelet count below 150 × 103/μL at baseline received a daily dose of 200 mg, while all other patients received a daily dose of 300 mg.

The results were significant. In the intention-to-treat population, the median PFS with niraparib was 24.8 months, compared with only 8.3 months with placebo (HR, 0.45; 95% CI, 0.34-0.60; P < .001). This reflects a reduced risk of disease progression or death by 55% for patients with newly diagnosed aOC being treat with niraparib, compared with placebo.

When analyzing subgroups based on germline BRCA variant status and tumor homologous recombination deficiency status, niraparib demonstrated consistent benefits. Patients with germline BRCA variants experienced a median PFS that was not reached with niraparib, compared with 10.8 months with placebo (HR, 0.40; 95% CI, 0.23-0.68). For patients without germline BRCA variants, the median PFS was 19.3 for niraparib and 8.3 months for placebo (HR, 0.48; 95% CI, 0.34-0.67).

Additionally, patients who were homologous recombination deficient had a median PFS that was not reached for niraparib and 11 months for placebo (HR, 0.48; 95% CI, 0.34-0.68), and patients who were proficient saw a median PFS of 16.6 months vs 5.5 months, respectively (HR, 0.41; 95% CI, 0.22-0.75). Finally, patients with optimal and suboptimal debulking had a 56% and 73% better PFS when they took niraparib compared with placebo, respectively.

The authors also found that the ISD was well-tolerated, with a similar proportion of patients in the niraparib (6.7%) and placebo (5.4%) groups discontinuing treatment due to treatment-emergent adverse events (TEAEs).

Similar proportions of patients in the PRIME and PRIMA placebo groups experienced grade 3 or higher TEAEs (17.8% vs 18.9%) and discontinued treatment due to TEAEs (5.4% vs 2.5%). However, patients from the PRIME niraparib group reported notably lower rates of grade 3 or higher TEAEs (54.5% vs 70.5%) and treatment discontinuation due to TEAEs (6.7% vs 12.0%) compared with their counterparts from the previous PRIMA trial.

There are several limitations worth noting. First, the study utilized a laboratory-developed, unvalidated HRD assay to determine tumor HRD status. However, despite this limitation, the authors said the homologous recombination status still had prognostic value, as demonstrated by a significantly shorter median PFS among patients who are homologous recombination proficient compared with patients who are homologous recombination-deficient. Additionally, the categorization of R0 and R1 resections as optimal debulking made it impossible to conduct subgroup analysis for patients with R0 resection, and the study solely focused on assessing efficacy and safety outcomes and not the impact of the treatment on patients' quality of life.

“The results of this randomized clinical trial support niraparib monotherapy as a standard of care after first-line platinum-based chemotherapy in a broad patient population with advanced ovarian cancer,” the authors concluded.

Reference

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 online July 13, 2023. doi:10.1001/jamaoncol.2023.2283