Abstract CT010: Efficacy results based on PIK3CA status in BELLE-3: A Phase 3 study of buparlisib (BKM120) + fulvestrant in postmenopausal women with aromatase inhibitor-treated, HR+/HER2- ABC after progression on an mTOR inhibitor

Introduction The phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is often activated in endocrine therapy (ET)-resistant, hormone receptor-positive (HR+) breast cancer (BC). Adding a PI3K inhibitor (PI3Ki) to ET may overcome ET or mTOR inhibitor (mTORi) resistance. In the Phase 3 BELLE-2 study, the pan-PI3Ki buparlisib (BUP) + fulvestrant (FULV) prolonged progression-free survival (PFS) in patients (pts) with HR+, human epidermal growth factor receptor 2-negative (HER2–) advanced BC (ABC), particularly in pts with PIK3CA mutations in circulating tumor DNA (ctDNA). Here, we report biomarker results from BELLE-3 (NCT01633060). Methods In total, 432 postmenopausal women with HR+/HER2– ABC who previously received an aromatase inhibitor and progressed on/within 30 days of ET + mTORi treatment were enrolled. Pts must not have received >1 chemotherapy regimen for ABC, or any prior PI3Ki, protein kinase B (AKT) inhibitor, or FULV. Pts were randomized 2:1 to receive BUP (100 mg/day) + FULV (500 mg) or placebo (PBO) + FULV, stratified by visceral disease status. PIK3CA status was assessed by BEAMing (exons 9 and 20 only) in plasma ctDNA collected at baseline, and in archival tumor samples by polymerase chain reaction (PCR) and next-generation sequencing (NGS). The primary endpoint was locally assessed PFS (RECIST v1.1). Secondary endpoints included overall survival, overall response rate, PFS by ctDNA PIK3CA status, quality of life, and safety; with exploratory PFS analyses by PIK3CA status in tumor tissue. Results BELLE-3 met its primary objective: PFS was significantly prolonged for BUP vs PBO, with hazard ratio (HR) 0.67 (95% confidence interval [CI]: 0.53–0.84; p