A Phase II study of the safety and efficacy of alpelisib or buparlisib plus letrozole in neoadjuvant treatment of postmenopausal women with HR+/HER2–, PIK3CA mutant or wild-type breast cancer.

TPS633 Background: The PI3K/AKT/mTOR pathway is the most frequently activated signaling pathway in breast cancer (BC). PIK3CA-activating mutations are the most common genetic alteration observed in hormone receptor-positive (HR+) BC. In preclinical studies of HR+ BC, alpelisib (PI3Kα inhibitor) and buparlisib (pan-PI3K inhibitor) demonstrated significant antitumor effects both in vitro and in vivo when combined with hormone therapy. Methods: A Phase II, randomized, double-blind, placebo-controlled trial of alpelisib/placebo (300 mg once daily [QD]) or buparlisib/placebo (100 mg QD; intermittent regimen [5 days on; 2 days off]) plus letrozole (2.5 mg QD) for the neoadjuvant treatment of postmenopausal women with HR+/HER2– BC (NCT01923168). Key inclusion criteria are stage T1c–T3, any N, M0 operable BC; measurable disease; HR+/HER2– BC; known PIK3CAstatus (mutant vs wild-type [WT]) and Ki67 level; and Eastern Cooperative Oncology Group performance status ≤ 1. Key exclusion criteria are locally recurrent/met...