Mirza MR, González-Martín A, Graybill WS, O'Malley DM, Gaba L, Stephanie Yap OW, Guerra EM, Rose PG, Baurain JF, Ghamande SA, Denys H, Prendergast E, Pisano C, Follana P, Baumann K, Calvert PM, Korach J, Li Y, Malinowska IA, Gupta D, Monk BJ
BACKGROUND : The PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trial was amended to prospectively evaluate the safety and efficacy of an individualized starting dose (ISD) regimen of niraparib for first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer.
METHODS : In the phase 3 PRIMA trial, patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy (N = 733) were initially treated with a fixed starting dose (FSD) regimen of 300 mg every day. Subsequently, the protocol was amended so newly enrolled patients received an ISD: 200 mg every day in patients with baseline body weight < 77 kg or baseline platelet count < 150,000/µL, and 300 mg every day in all other patients. Efficacy and safety outcomes were assessed by starting dose.
RESULTS : Overall, 475 (64.8%) patients were assigned to an FSD (niraparib, n = 317; placebo, n = 158) and 258 (35.2%) were assigned to an ISD (niraparib, n = 170; placebo, n = 88). Efficacy in patients who received FSD or ISD was similar for the overall (FSD hazard ratio [HR], 0.59 [95% CI, 0.46-0.76] vs. ISD HR, 0.69 [95% CI, 0.48-0.98]) and the homologous recombination-deficient (FSD HR, 0.44 [95% CI, 0.30-0.64] vs. ISD HR, 0.39 [95% CI, 0.22-0.72]) populations. In patients with low body weight/platelet count, rates of grades ≥3 and 4 hematologic treatment-emergent adverse events, dose interruptions, and dose reductions were lower for those who received ISD than for those who received FSD.
CONCLUSIONS : In PRIMA, similar dose intensity, similar efficacy, and improved safety were observed with the ISD compared with the FSD regimen.