Prospective evaluation of the tolerability and efficacy of niraparib dosing based on baseline body weight and platelet count: Results from the PRIMA/ENGOT-OV26/GOG-3012 trial
Mansoor R Mirza 1 , Antonio González-Martín 2 3 , Whitney S Graybill 4 , David M O'Malley 5 , Lydia Gaba 6 , Oi Wah Stephanie Yap 7 , Eva M Guerra 8 , Peter G Rose 9 , Jean-François Baurain 10 , Sharad A Ghamande 11 , Hannelore Denys 12 , Emily Prendergast 13 , Carmela Pisano 14 , Philippe Follana 15 , Klaus Baumann 16 , Paula M Calvert 17 , Jacob Korach 18 , Yong Li 19 , Izabela A Malinowska 19 , Divya Gupta 19 , Bradley J Monk 20
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.
CITATION Cancer. 2023 Apr 14. doi: 10.1002/cncr.34706