AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) has been approved in the US for the treatment of adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN). The approval by the Food and Drug Administration (FDA) was based on the results from the CAPItello-291 Phase III trial...

Compared with fulvestrant alone, the addition of capivasertib to fulvestrant provided a consistent PFS benefit across alterations in all three key genes within the AKT pathway in patients with HR-positive/HER2 negative ABC.

AstraZeneca’s New Drug Application (NDA) for capivasertib in combination with Faslodex (fulvestrant) has been accepted and granted Priority Review in the US for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer following recurrence or progression on or after an endocrine-based regimen.

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.

At the RP3D, the median (range) duration of exposure to C was 8.6 months (1.7–14.1); 5/8 pts with measurable disease at baseline had confirmed partial response (objective response rate: 62.5%, 95% confidence interval [CI] 24.5–91.5). Two additional pts had stable disease ≥7 weeks as a best objective response...C+P+F was tolerable in heavily pre-treated pts with HR+/HER2– ABC at all dose levels...