Aims: We summarize niraparib efficacy and safety in patients with BRCAm OC across three phase 3 trials: PRIMA/ENGOT-OV26/GOG-3012 (PRIMA; NCT02655016), ENGOT-OV16/NOVA (NOVA; NCT01847274), and NORA (NCT03705156).
Methods: Patients in PRIMA had newly diagnosed advanced OC. All had stage III/IV high-grade serous or endometrioid tumors and complete/partial response to first-line platinum-based CT. Subgroup analysis by tumor BRCAm status was prespecified.
Patients in NOVA and NORA had platinum-sensitive, high-grade serous OC. Patients had received ≥2 lines of platinum-based CT. In both, subgroup analysis by germline BRCAm status was prespecified.
Primary endpoint in all was progression-free survival (PFS) by blinded independent central review.
Results: BRCAm populations from each were: 223 (148 BRCA1m and 75 BRCA2m) from PRIMA, 203 (128 BRCA1m, 69 BRCA2m, and 13 BRCA1/2m) from NOVA, and 100 (78 BRCA1m, 21 BRCA2m, and 1 BRCA1/2m) from NORA. PFS results are shown (Table). Across the trials, the most common treatment-emergent adverse events were thrombocytopenia, anemia, neutropenia, and hypertension.
Conclusions: Patients with BRCAm OC derived significant PFS benefit from niraparib maintenance treatment across all 3 trials. No new safety signals were identified.
|
Trial |
n |
Niraparib mPFS, months |
Placebo mPFS, months |
HR (95% CI) |
|
PRIMA |
||||
|
BRCAm FSD ISD BRCA1 BRCA2 |
223 144 79 148 75 |
22.1 22.1 14.8 19.6 NR |
10.9 11.1 10.9 8.4 13.6 |
0.40 (0.27–0.62) 0.44 (0.26–0.73) 0.29 (0.13–0.67) 0.39 (0.23–0.66) 0.35 (0.15–0.84) |
|
NOVA |
||||
|
gBRCAm BRCA1 BRCA2 |
203 128 69 |
21.0 12.9 NR |
5.5 5.8 5.4 |
0.27 (0.17–0.41) 0.39 (0.23–0.66) 0.12 (0.05–0.33) |
|
NORAa |
||||
|
gBRCAm |
100 |
NR |
5.5 |
0.22 (0.12–0.39) |
|
aBRCA1 and BRCA2 data not currently available. FSD, fixed starting dose; HR, hazard ratio; ISD, individualized starting dose; mPFS, median PFS; NR, not reached. |