Abstract RF7-02: Alpelisib plus fulvestrant for PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer after a CDK4/6 inhibitor (EPIK-B5): Phase III, randomized, double-blind, placebo-controlled, multicenter study

Abstract Background: Alpelisib (ALP), an α-specific PI3K inhibitor, plus fulvestrant (FUL) improved disease control with a manageable safety in patients (pts) with HR+, HER2− advanced breast cancer (ABC) harboring a PIK3CA-m in SOLAR-1 and in BYLieve Cohort A trials. We report primary results from the EPIK-B5 study, comparing ALP+FUL vs placebo (PBO)+FUL in men/postmenopausal women with PIK3CA-m HR+, HER2− ABC who had progressed on cyclin-dependent kinase 4/6 inhibitor (CDK4/6i)+aromatase inhibitor (AI). Methods: EPIK-B5 was a phase 3, double-blind, PBO-controlled study. Pts (n=188) were randomised 1:1 to ALP+FUL (arm 1) or PBO+FUL (arm 2). The primary endpoint was progression-free survival (PFS) by Blinded Independent Review Committee [BIRC]. Secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), time to response (TTR), PFS by PIK3CA-m in baseline ctDNA, adverse events (AEs), time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status, change in global health status and symptom scale scores of the EORTC QLQ-C30, and time to progression on next line treatment or death (PFS2) by investigator assessment. Results: Baseline characteristics are shown in the Table. At primary analysis (data cutoff Oct 2024), median follow-up duration was 17.7 (1.4-33.1) months (mo). The median PFS (BIRC) was 7.4 and 2.8 mo in arm 1 and 2, respectively, (HR: 0.52, 95% CI: 0.37,0.72, log-rank p