Clinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) after prior treatment (tx) with FUL in patients (pts) with advanced breast cancer (ABC): A real-world (RW) analysis.

1055 Background: ALP (α-selective PI3K inhibitor and degrader) + FUL was FDA approved and reflected in the NCCN guidelines in 2019 for pts with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) ABC with PIK3CA mutations following progression on or after endocrine-based therapy (ET). The Phase III SOLAR-1 trial excluded prior FUL, and data on ALP + FUL after FUL are limited. As cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + ET (including FUL) is the standard in the first line (1L) or second line (2L) for pts with HR+/HER2− ABC, more data on ALP + FUL post-FUL are needed. Here we report patterns and clinical outcomes on RW use of ALP + FUL in pts with HR+/HER2– ABC with prior FUL exposure. Methods: This retrospective study used de-identified electronic health record data from the ConcertAI Patient360 Breast Cancer data product sourced from US oncology centers. Adults with HR+/HER2− ABC treated with ALP + FUL (index tx) who received prior FUL (monotherapy or in combination) in the metastatic setting were included; pts with a PIK3CA negative test on or prior to the index were excluded. Pts were followed until date of death or last activity. RW progression-free survival (rwPFS), defined as first documented progression/death from ALP + FUL start date, was assessed. Results: This analysis included 157 pts (median age, 63 y [57-71 y]) who received ALP + FUL from 2019 to 2021, with 11.5% pts in 1L, 17.8% in 2L, 26.8% in third line (3L), and 43.9% in fourth line and beyond (4L+). Prior FUL tx included CDK4/6i + FUL (74.5%), FUL alone (33.8%), and non-CDK4/6i + FUL (21.0%). In pts who received ALP + FUL in 1L (n = 18), prior FUL exposure was in the same line without documented progression. In the metastatic setting, 28.0% of pts received > 1 FUL-containing regimen and/or 72.0% received prior chemotherapy (CT). At the median duration of follow-up (8.7 mo [4.1-12.5 mo]), the median rwPFS was 5.7 mo (4.0-7.3 mo) in the overall population. The median rwPFS was also analyzed by line of therapy (Table). In pts with CDK4/6i + FUL as immediate prior therapy (n = 39), the median rwPFS was 6.2 mo (3.0-9.1 mo); 79.5% of these pts received ALP in ≤ 3L. At the time of analysis, 107 pts (68.2%) had discontinued ALP + FUL; the median time to discontinuation was 4.7 mo (3.7-6.1 mo). Following discontinuation of ALP + FUL, CT was the most common subsequent therapy (33.8%). Conclusions: This analysis on RW data from early years of ALP access in the US shows clinical benefit of ALP + FUL in pts with HR+/HER2− ABC with PIK3CA mutation even when exposed to prior FUL, confirming the oncogenic dependence of the tumor on the PIK3CA mutation. [Table: see text]