Rucaparib for BRCA1/2-mutated pretreated ovarian cancer: reflections from the ARIEL4 trial
Mené sur 349 patientes atteintes d'un cancer de l'ovaire récidivant et présentant des mutations BRCA (âge médian : 58 ans), cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du rucaparib par rapport à une chimiothérapie avec ou sans sels de platine
The discovery that homologous recombination deficiency (HRD), a DNA repair defectpresent in tumours with BRCA1 or BRCA2 (BRCA1/2) mutations, can prevent affected cells from overcoming replicative or drug-inducedDNA double-strand breaks both suggested a new therapeutic possibility and explainedthe observed heterogeneity of chemotherapy effectiveness in women with ovarian cancer.Oral PARP inhibitors were predictably active against BRCA1/2-mutated tumours, by disrupting other DNA repair mechanisms, an effect known as synthetic lethality. It turned out that tumours in the subgroupof women who have excellent and repeated responses to platinum were often characterisedby BRCA1/2 mutations—although, sadly, as with almost all ovarian cancers, with HRD or not, platinumresponsiveness eventually wanes.
The Lancet Oncology , commentaire, 2021