Abstract RF7-05: Capivasertib plus fulvestrant in hormone receptor-positive (HR+) advanced breast cancer (ABC): exploratory ctDNA analyses from the Phase 3 CAPItello-291 trial

Abstract Background: Based on the results of the global Phase 3 CAPItello-291 trial, the pan-AKT inhibitor capivasertib (C) is recommended in combination with fulvestrant (F) for patients (pts) with PIK3CA/AKT1/PTEN-altered HR+ ABC progressing after ≥1 line of endocrine therapy-based treatment. The primary analysis showed clinically meaningful improvement in progression-free survival (PFS) in both overall and PIK3CA/AKT1/PTEN-altered populations (identified based on tumor sequencing) treated with C + F vs placebo (pbo) + F. Here, we report exploratory ctDNA analyses. Methods: Eligible pts with HR+/HER2- ABC had progression ≤12 months of (neo)adjuvant aromatase inhibitor (AI) treatment, or while on prior AI-based treatment for ABC. Pts were randomized 1:1 to C + F or pbo + F. PIK3CA/AKT1/PTEN alteration status was determined in tumor tissue collected at study entry assessed by FoundationOne®CDx NGS, and in baseline blood samples for ctDNA analysis using Guardant InfinityTM which also reports methylation-based ctDNA tumor fraction (TF). Results: Of 708 pts in the overall population, 658 (92.9%) had a ctDNA sample for analysis. Overall concordance between ctDNA and tissue was 83.3% (Table). No/low shedding (TF