Progression-free survival and safety at 3.5 years of follow-up: results from the randomized phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer - a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This PLSP provides a short summary of an original scientific article that presented results from the PRIMA study after 3.5 years of follow-up time. The original article was published in the European Journal of Cancer in 2023. The PRIMA study included adult patients with newly diagnosed advanced high-risk ovarian cancer whose tumors shrunk or became undetectable after treatment with chemotherapy with or without surgery. The PRIMA study evaluated how well the drug niraparib, also known as Zejula, worked at delaying or preventing ovarian cancer from coming back (recurring) or getting worse (progressing) compared with placebo (a substance with no effects that a doctor gives to a patient instead of a drug). The first results from the PRIMA study were published in 2019, when patients had participated in the PRIMA study for about 1.2 years. The article this PLSP is based on reports longer-term data from the PRIMA study, when patients had participated in the PRIMA study for about 3.5 years. Patients were monitored (or followed) for a longer time to understand how well niraparib continued to work and to evaluate whether the safety of niraparib changed with additional time being monitored. WHAT WERE THE RESULTS?: Patients who took niraparib had more time before their cancer came back or got worse than patients who took placebo. In terms of safety, no new types of side effects with niraparib treatment were observed with additional time being monitored as part of the PRIMA study. WHAT DO THE RESULTS MEAN?: These results support that niraparib remains an important treatment option to help delay the cancer from coming back or getting worse in patients with newly diagnosed advanced ovarian cancer that responded to initial treatment. Clinical Trial Registration: NCT02655016 (PRIMA study) (ClinicalTrials.gov).

A Relative Bioavailability, Bioequivalence, and Food Effect Study of Niraparib Tablets in Patients with Advanced Solid Tumors.

PURPOSE: The poly (ADP-ribose) polymerase inhibitor niraparib is indicated as maintenance treatment in patients with certain subtypes of advanced ovarian cancer, and is being investigated in patients with other solid tumors. Niraparib is available in 100-mg capsules with a starting dosage of 200 or 300 mg/d. This study assessed the relative bioavailability (BA) and bioequivalence (BE) between a 1 × 300-mg tablet relative to 3 × 100-mg niraparib capsules. In addition, the food effect (FE) of a high-fat meal on the pharmacokinetic (PK) properties of tablet-formulated niraparib was investigated. METHODS: This was a US-based, 3-stage, open-label, multicenter, single-crossover, randomized-sequence study. Enrolled patients were 18 years and older, with histologically or cytologically confirmed advanced solid tumors (metastatic or local) and disease progression despite standard therapy. Patients were randomly assigned 1:1 to receive niraparib 1 × 300-mg tablet or 3 × 100-mg capsules in the BA and BE stages or 1 × 300-mg tablet in a fasted or fed (high-fat meal) state in the FE stage. Across all study stages, PK parameters were assessed for 7 days after each dose (tablet or capsule) or prandial state (fasted or fed). In the BA stage, patients crossed over to the other treatment after a 7-day washout period, which was extended to 14 days in the BE and FE stages. Tolerability was assessed for patients who received any amount of niraparib. FINDINGS: The BA-, BE-, and FE-evaluable populations comprised 23, 108, and 19 patients, respectively, who completed both treatment periods in each study stage, had sufficient concentration data to accurately estimate PK parameters without niraparib carryover, and did not experience disqualifying events. PK parameters were similar after dosing with tablet or capsule formulations; the 90% CIs of the geometric least square means for Cmax, AUC0-t, and AUC0-∞ were within the 0.80 to 1.25 BE limits. In the FE stage, Cmax, AUC0-t, and AUC0-∞ were 11%, 32%, and 28% higher, respectively, in the fed versus fasted state. The safety population included 29, 168, and 28 patients in the BA, BE, and FE stages, respectively, who received niraparib. No new safety signals were identified. IMPLICATIONS: Niraparib tablets were found to be bioequivalent to capsules. A modest (≤32%) FE was observed with a high-fat meal, but was not considered to be clinically meaningful, given niraparib's PK variability. CLINICALTRIALS: gov identifier: NCT03329001. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc.

Progression-free survival and safety at 3.5years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer.

PURPOSE: To report updated long-term efficacy and safety from the double-blind, placebo-controlled, phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016). METHODS: Patients with newly diagnosed advanced ovarian cancer with complete or partial response (CR or PR) to first-line platinum-based chemotherapy received niraparib or placebo once daily (2:1 ratio). Stratification factors were best response to first-line chemotherapy regimen (CR/PR), receipt of neoadjuvant chemotherapy (yes/no), and homologous recombination deficiency (HRD) status (deficient [HRd]/proficient [HRp] or not determined). Updated (ad hoc) progression-free survival (PFS) data (as of November 17, 2021) by investigator assessment (INV) are reported. RESULTS: In 733 randomised patients (niraparib, 487; placebo, 246), median PFS follow-up was 3.5years. Median INV-PFS was 24.5 versus 11.2months (hazard ratio, 0.52; 95% confidence interval [CI], 0.40-0.68) in the HRd population and 13.8 versus 8.2months (hazard ratio, 0.66; 95% CI, 0.56-0.79) in the overall population for niraparib and placebo, respectively. In the HRp population, median INV-PFS was 8.4 versus 5.4months (hazard ratio, 0.65; 95% CI, 0.49-0.87), respectively. Results were concordant with the primary analysis. Niraparib-treated patients were more likely to be free of progression or death at 4years than placebo-treated patients (HRd, 38% versus 17%; overall, 24% versus 14%). The most common grade ≥ 3 treatment-emergent adverse events in niraparib patients were thrombocytopenia (39.7%), anaemia (31.6%), and neutropenia (21.3%). Myelodysplastic syndromes/acute myeloid leukaemia incidence rate (1.2%) was the same for niraparib- and placebo-treated patients. Overall survival remained immature. CONCLUSIONS: Niraparib maintained clinically significant improvements in PFS with 3.5years of follow-up in patients with newly diagnosed advanced ovarian cancer at high risk of progression irrespective of HRD status. No new safety signals were identified.