Pooled analysis data from the PRIMA, NOVA, and NORA trials suggest that patients with BRCA-mutated ovarian cancer derive a significant progression-free survival benefit from niraparib maintenance treatment, with no new safety signals.
Results of pooled analysis of 3 phase 3 trials that evaluated efficacy and safety of the poly (ADP-ribose) polymerase (PARP) inhibitor, niraparib, in patients with ovarian cancer harboring BRCA mutations were presented at the 2021 American Society of Clinical Oncology Annual Meeting. Trials considered in the analysis were PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016), ENGOT-OV16/NOVA (NCT01847274), and NORA (NCT03705156).
The pooled analysis included patients enrolled in 3 phase 3 trials: PRIMA, NOVA, and NORA. The PRIMA trial enrolled patients with newly diagnosed advanced ovarian, fallopian tube, or primary peritoneal cancer who had stage III or IV high-grade serous or endometrioid tumors and a complete or partial response to their first-line platinum-based chemotherapy. Both the NOVA and NORA trials enrolled patients with platinum-sensitive, advanced ovarian, fallopian tube, or primary peritoneal cancer who had received ≥2 lines of platinum-based chemotherapy. Prespecified subgroup analysis in the PRIMA trial was by tumor BRCA mutation status, and by germline BRCA mutation status in the NOVA and NORA trials. In all 3 trials, the primary end point was progression-free survival (PFS) by blinded independent central review.
Overall, a total of 526 patients enrolled in the PRIMA, NOVA, and NORA trials had BRCA mutations. Of these, 223 patients were enrolled in the PRIMA trial, 203 in the NOVA trial, and 100 in the NORA trial. The majority of BRCA mutations were in the BRCA1 gene (PRIMA: 148 BRCA1m, 75 BRCA2m; NOVA: 128 BRCA1m, 69 BRCA2m, and 13 BRCA1/2m; NORA: 78 BRCA1m, 21 BRCA2m, and 1 BRCA1/2m).
Patients with ovarian cancer harboring BRCA mutations had a significant PFS advantage with niraparib maintenance treatment in the PRIMA trial (BRCAm, 22.1 vs 10.9 months; hazard ratio [HR], 0.40), NOVA trial (gBRCAm, 21.0 vs 5.5 months; HR, 0.27), and NORA trial (gBRCAm, not estimable vs 5.5 months; HR, 0.22), showing a trend that was consistent for both BRCA1 and BRCA2 mutations. Across the 3 trials, the most frequent treatment-emergent adverse events were thrombocytopenia, anemia, neutropenia, and hypertension.
Pooled analysis data from the PRIMA, NOVA, and NORA trials indicate that patients with BRCAm ovarian cancer derive a significant PFS benefit from niraparib maintenance treatment, with the emergence of no new safety signals.
Source: Martin AG, Matulonis UA, Korach J, et al. Niraparib efficacy and safety in patients with BRCA mutated (BRCAm) ovarian cancer: results from three phase 3 niraparib trials. J Clin Oncol. 2021;39(suppl_15). Abstract 5518.