Abstract PS5-07-03: Capitrue, capicorn, and capitana: three phase iiib studies to evaluate the use of capivasertib in combination with fulvestrant in patients with advanced breast cancer who have relapsed/progressed on endocrine therapy and cdk4/6 inhibitors reflecting real-world clinical practice in china, germany, belgium, portugal and spain

Abstract HR+/HER2− advanced breast cancer (ABC) remains a therapeutic challenge due to resistance to endocrine therapy (ET) and CDK4/6 inhibitors. Alterations in the PI3K/AKT pathway, including PIK3CA, AKT1, and PTEN alterations, are associated with poor prognosis and with the activation of PI3K-AKT signaling. Capivasertib, a selective AKT inhibitor, improved progression free survival (PFS) statistically significant and clinically meaningful in the CAPItello291 trial (NCT04305496), when combined with fulvestrant, both in the overall population (PFS in Capivasertib+fulvestrant group 7.2 vs 3.6 in placebo+fulvestrant group, HR=0.60) and in patients with PIK3CA/AKT1/PTEN altered tumors (PFS in Capivasertib+fulvestrant group 7.3 vs 3.1 in placebo+fulvestrant group, HR=0.50). Building on these findings, the CAPItrue (China-NCT06635447), CAPIcorn (Germany, Belgium, and Portugal), and CAPItana (Spain-NCT06764186) trials aim to evaluate the real-world (RW) effectiveness and safety in five countries, addressing the need for region specific data to inform clinical practice and treatment strategies in diverse healthcare settings. Based on CAPItello291 trial protocol, the CAPItrue (China), CAPIcorn (Germany, Belgium, and Portugal), and CAPItana (Spain) studies are Phase IIIb, single arm, multicenter trials designed to evaluate in a RW setting the effectiveness and safety of the combination. All studies administer capivasertib 400 mg BID (4 days on, 3 days off) together with fulvestrant (FUL) 500 mg IM every 28 days, with a loading dose given on Day 15 of Cycle 1, in patients with HR+/HER2- advanced breast cancer and alterations in PIK3CA/AKT1/PTEN who have progressed on ET in combination with CDK4/6 inhibitors. CAPItrue uniquely allows inclusion of patients without PI3K/AKT pathway alterations. Inclusion criteria allow for up to two previous lines of ET (and one line of chemotherapy for advanced disease), include diabetic or prediabetic patients (HbA1c