Multinational phase 3 trial of capivasertib plus fulvestrant for AI-resistant HR-positive/HER2-negative advanced breast cancer

AKT pathway activation has been implicated in the development of endocrine therapy resistance in HR-positive/HER2-negative advanced breast cancer (ABC). Capivasertib is a pan-AKT inhibitor. The multinational phase 3 CAPItello-291 trial evaluated addition of capivasertib versus placebo to fulvestrant in patients with HR+/HER2- ABC that had recurred or progressed on or after AI therapy with or without a CDK4/6 inhibitor. The median PFS was 7.2 months with capivasertib plus fulvestrant versus 3.1 months with placebo plus fulvestrant (HR 0.60; p<0.001). Among patients with AKT pathway altered tumors the median PFS was 7.3 months versus 3.1 months (HR 0.50; pxtagstartz0.001). Adverse events leading to discontinuation of capivasertib/placebo were reported in 13.0% and 2.3% of patients, respectively. The authors conclude that capivasertib plus fulvestrant may become a treatment option in this setting.