Targeting PIK3CA-mutant advanced breast cancer in the clinical setting
Mené dans 29 pays sur 1 147 patientes atteintes d'un cancer du sein ER+, HER2- de stade avancé après la ménopause, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du buparlisib, un inhibiteur de PI3K, au fulvestrant, après l'échec d'un traitement par inhibiteur de l'aromatase
Activation mutations in PIK3CA are the most common genetic event in hormone receptor-positive breast cancer. PIK3CA encodes the p110
α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), and activation of the PI3K
–AKT–mTOR pathway promotes disease progression and resistance to endocrine therapy. PIK3CA mutant cancer models are sensitive to PI3K inhibitors preclinically, with synergy occurring between PI3K inhibitors and endocrine therapies. Yet, despite convincing preclinical data, several early-phase and randomised phase 2 studies have failed to show a significant benefit of PI3K inhibitors in PIK3CA-mutant cancers, which brings into question whether PIK3CA mutations are targetable in the clinic.
The Lancet Oncology , commentaire, 2016