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.

Abstract

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 once daily. Subsequently, the protocol was amended so newly enrolled patients received an ISD: 200 mg once daily in patients with baseline body weight < 77 kg or baseline platelet count < 150,000/µL, and 300 mg once daily 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.

• Authors: Mansoor R Mirza, Antonio González-Martín, Whitney S Graybill, David M O'Malley, Lydia Gaba, Oi Wah Stephanie Yap, Eva M Guerra, Peter G Rose, Jean-François Baurain, Sharad A Ghamande, Hannelore Denys, Emily Prendergast, Carmela Pisano, Philippe Follana, Klaus Baumann, Paula M Calvert, Jacob Korach, Yong Li, Izabela A Malinowska, Divya Gupta, Bradley J Monk
• Journal: Cancer (Cancer) Vol. 129 Issue 12 Pg. 1846-1855 (06 15 2023) ISSN: 1097-0142 [Electronic] United States
• PMID: 37060236 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

Chemical References

• Indazoles
• niraparib
• Poly(ADP-ribose) Polymerase Inhibitors

Topics

• Female
• Humans
• Body Weight
• Carcinoma, Ovarian Epithelial (drug therapy)
• Indazoles
• Ovarian Neoplasms (drug therapy)
• Poly(ADP-ribose) Polymerase Inhibitors (therapeutic use)
• Prospective Studies