Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from PRIMA/ENGOT-OV26/GOG-3012 trial
Mené sur 733 patientes atteintes d'un cancer de l'ovaire de stade avancé, récemment diagnostiqué et ayant répondu favorablement à une chimiothérapie de première ligne à base de sels de platine (durée médiane de suivi : 73,9 mois), cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité du niraparib en traitement d'entretien
Résumé en anglais
Background: The phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial met its primary endpoint. Niraparib first-line maintenance significantly prolonged progression-free survival (PFS) among patients with newly diagnosed advanced ovarian cancer (aOC) that responded to first-line platinum-based chemotherapy, regardless of homologous recombination deficiency (HRD) status. Final overall survival (OS) results are reported.
Patients and methods: Patients were randomized 2:1 to niraparib or placebo, stratified by response to first-line treatment, receipt of neoadjuvant chemotherapy, and tumor HRD status. After reaching 60% target maturity, OS was evaluated via a stratified log-rank test using randomization stratification factors and summarized using Kaplan–Meier methodology. OS testing was hierarchical (overall population first, then the homologous recombination-deficient [HRd] population). Other secondary outcomes and long-term safety were assessed; an updated, ad hoc analysis of investigator-assessed PFS was also conducted (cutoff date, 08Apr2024).
Results: Median follow-up was 73.9 months. In the overall population, the OS hazard ratio (HR) was 1.01 (95% CI, 0.84-1.23; P= 0.8834) for niraparib (n= 487) versus placebo (n;= 246). In the HRd (n= 373) and homologous recombination-proficient (n= 249) populations, the OS HRs were 0.95 (95% CI, 0.71-1.29) and 0.93 (95% CI 0.69-1.26), respectively. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 11.7% and 15.8% of niraparib patients and 37.8% and 48.4% of placebo patients in the overall and HRd populations, respectively. The 5-year PFS rate numerically favored niraparib in the overall (niraparib, 22%; placebo, 12%) and HRd populations (niraparib, 35%; placebo, 16%). Myelodysplastic syndromes/acute myeloid leukemia incidence was <2.5% (niraparib, 2.3%; placebo, 1.6%). No new safety signals were observed.
Conclusions: In patients with newly diagnosed aOC at high risk of recurrence, there was no difference in OS between treatment arms. In the HRd population, patients alive at 5 years were twice as likely to be progression free with niraparib treatment than placebo. Long-term safety remained consistent with the established niraparib safety profile.
