Overall Survival and the Evolving Benefit-Risk Assessment for Poly (ADP-ribose) Polymerase Inhibitors in Advanced Ovarian Cancer
Cet article décrit le processus décisionnel de la "US Food and Drug Administration" et les raisons justifiant le retrait des inhibiteurs de PARP ou la restriction de leurs indications pour le traitement des cancers épithéliaux de l'ovaire de stade avancé
From 2014 through 2019, the US Food and Drug Administration (FDA) granted approval to six indications for poly (ADP-ribose) polymerase (PARP) inhibitors in advanced epithelial ovarian cancer (EOC). From 2022 through 2023, these six indications were withdrawn or narrowed after observation of a potential detrimental effect on overall survival (OS) in four randomized controlled trials. The indications for niraparib, olaparib, and rucaparib for the treatment of BRCA-mutated or homologous recombination deficiency–positive advanced EOC were withdrawn. The indications for niraparib, olaparib, and rucaparib for the maintenance treatment of recurrent EOC were narrowed to only patients with BRCA mutations. Recognizing the clinical implications of these regulatory actions, herein we describe the FDA's decision-making process and the rationale behind the removal or narrowing of these indications for PARP inhibitors in advanced EOC. Furthermore, this article provides insight into the FDA's interpretation of potential OS detriments and subgroup analyses to shape regulatory decisions.
Journal of Clinical Oncology , résumé, 2025