Dostarlimab and niraparib in primary advanced ovarian cancer
Mené sur 1 138 patientes atteintes d'un cancer épithélial de l'ovaire de stade avancé (durée médiane de suivi : 53,1 mois), cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de dostarlimab à un traitement d'entretien de première ligne combinant une chimiothérapie à base de sels de platine et du niraparib
Background: The combination of immunotherapies and poly (ADP-ribose) polymerase inhibitors (PARPis) has been hypothesized to improve outcomes in advanced ovarian cancer (aOC). The FIRST/ENGOT-OV44 trial evaluated adding dostarlimab to first-line platinum-based chemotherapy (PBCT) and niraparib maintenance ± bevacizumab in patients with aOC.
Patients and methods: In this randomized, double-blind, phase III trial, patients with newly diagnosed stage III-IV epithelial OC were randomized (1:2) to arm 2 (PBCT–placebo with niraparib maintenance) or arm 3 (PBCT–dostarlimab with dostarlimab–niraparib maintenance); arm 1 (PBCT–placebo with placebo maintenance) enrollment terminated following PARPi approvals. Efficacy was assessed in arms 2 and 3 (intention-to-treat population). The primary endpoint was investigator-assessed progression-free survival (PFS) as per RECIST v1.1. The key secondary endpoint was overall survival (OS). Safety was assessed in patients who received one or more doses of study treatment (arms 1-3; analyzed as per treatment received).
Results: From 14 November 2018 to 5 January 2021, 1138 patients were randomized to arms 2 (n = 385) and 3 (n = 753) and included in efficacy analyses. Median follow-up was 53.1 (interquartile range 47.5-59.7) months. There was a statistically significant difference in PFS in arm 3 versus arm 2 (median 20.6 versus 19.2 months; hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.73-0.99, P = 0.0351). OS had reached 57% maturity and was not statistically significant (median 44.4 versus 45.4 months; HR 1.01, 95% CI 0.86-1.19, P = 0.9060). Toxicities observed were consistent with known safety profiles of the agents used in the study.
Conclusions: In the first-line treatment of patients with aOC, the addition of dostarlimab to PBCT and niraparib maintenance was associated with a statistically significant, but clinically modest, PFS improvement, with no difference in OS.
Annals of Oncology , résumé, 2025