Immune Checkpoint and Poly(ADP–Ribose) Polymerase Inhibition for Recurrent Platinum-Resistant Ovarian and Metastatic Triple-Negative Breast Cancers
Mené sur 62 patientes atteintes d'un cancer de l'ovaire résistant aux sels de platine et récidivant (âge médian : 60 ans) et sur 55 patientes atteintes d'un cancer du sein triple négatif de stade avancé ou métastatique (âge médian : 54 ans), cet essai de phase I/II évalue la dose maximale tolérée du niraparib en combinaison avec le pembrolizumab, puis évalue l'efficacité de ce traitement, du point de vue du taux de réponse objective
Patients with recurrent platinum-resistant ovarian carcinoma (PROC) or metastatic triple-negative breast cancer (TNBC) have a poor prognosis, and effective management remains a large unmet medical need. Recent advances in multiomic analyses of cancers have uncovered molecular similarities between these 2 clinically distinct entities. In particular, The Cancer Genome Atlas Research Network revealed marked genomic similarities between TNBC and the most frequent ovarian cancer subtype, high-grade serous ovarian carcinoma. Both subtypes exhibit a very high frequency of TP53 (OMIM 191170) mutations, BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) inactivation, and copy number gains and losses.1 These molecular features suggest that similar biological mechanisms drive some aspects of both cancer types, which in turn may direct their treatment strategies. In addition, high-grade serous ovarian carcinoma and TNBC are potentially immunoreactive tumors, based on observations indicating that the presence of intraepithelial tumor-infiltrating lymphocytes is associated with improved clinical outcomes.(...)
JAMA Oncology 2019