In a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer...were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant….Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor.

Pts were randomised 1:1 to receive fulv (500 mg IM on days 1 and 15 of cycle 1, and day 1 of each subsequent 28-day cycle) with either placebo or capivasertib (400 mg twice daily; 4 days on, 3 days off)….PFS benefit of capivasertib-fulv over placebo-fulv was broadly consistent across key clinical subgroups (Table)....Exploratory PFS analyses confirmed a consistent benefit of treatment with capivasertib-fulv vs fulv alone in clinically relevant subgroups, including pts with prior CDK4/6i exposure or liver metastases, subgroups with poor prognosis on fulv alone.