Maintenance Niraparib Extended PFS Among Patients With Advanced Ovarian Cancer
Results From the Phase 3 PRIME Study
Results From the Phase 3 PRIME Study
Results from this phase 3 study demonstrated that niraparib, a potent, highly selective PARP inhibitor, prolonged progression-free survival (PFS) among patients with newly diagnosed advanced ovarian cancer, regardless of postoperative residual disease or biomarker status, with an individualized starting dose (ISD) that is both safe and effective in the first-line maintenance setting.
According to Ning Li, MD, National Cancer Center, Beijing, China and coauthors, prior evidence from “The phase 3 PRIMA study demonstrated that niraparib..significantly prolonged PFS vs placebo in the first-line maintenance setting regardless of [homologous recombination deficiency] status” however, “The efficacy and safety of niraparib with ISD still need further prospective assessment.”
In this double-blind, placebo-controlled study, 759 patients with newly diagnosed, advanced ovarian cancer, who previously received primary interval debulking surgery and responded to first-line platinum-based chemotherapy, were randomized on a 2-to-1 basis to receive either niraparib (n = 502) or placebo (n = 257). Randomization was stratified based on germline BRCA variant status, tumor homologous recombination deficiency (HRD) status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy. Patients with a body weight under 77 kg and/or a platelet count under 150 x 103/μL at baseline received 200 mg niraparib (n = 247) or matched placebo (n = 128) orally once daily. All other patients received 300 mg niraparib (n = 255) or matched placebo (n = 129) orally once daily. Treatment was administered in 28-day cycles for up to 36 months until disease progression, intolerable toxic effects, withdrawal, loss of follow-up, or death. The primary end point was PFS among the intention-to-treat (ITT) population with secondary end points including overall survival (OS) and time to first subsequent anticancer therapy in the ITT population, as well as PFS and OS of the HRD subgroup (including patients with germline BRCA variants, positive tumor HRD status, or both.)
At the data cutoff date of September 30, 2021, the median follow-up was 27.5 months. In the ITT population the median PFS was 24.8 months in the niraparib arm and 8.3 months in the placebo arm (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.34 to 0.60; P < .001). The time to first subsequent anticancer therapy was 26.2 months in the niraparib arm and 11.9 months in the placebo arm (HR, 0.45; 95% CI, 0.34 to 0.59; P < .001). Data for OS in the ITT population was not yet mature. In the HRD subgroup, the median PFS was not reached among patients treated with niraparib vs 11.0 months with placebo (HR, 0.48; 95% CI, 0.34 to 0.68).
Most treatment-emergent adverse events were well-controlled and a similar proportion of patients in both arms discontinued treatment due to a treatment-emergent adverse event. The most common grade ≥3 treatment-emergent adverse events were, anemia, neutrophil count decrease, platelet count decrease, and white blood cell count decrease.
As Dr Li and coauthors concluded, “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.”
Source: Li N, Zhu J, Yin R, et al. Treatment with niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer. JAMA Oncol. Published online July 13, 2023. doi:10.1001/jamaoncol.2023.2283
