Clinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) in patients with HR-positive (HR+)/HER2-negative (HER2-) advanced breast cancer (ABC) with PIK3CA mutations (m) in routine practice at several Russian centers

e13053 Background: The data of ALP efficacy after FUL, chemotherapy (CT) and in later lines is limited. Only a small percentage of pts in BYLieve trial in cohort C received FUL (32%), CT (37%) and received ALP in later lines (only 4 pts received ALP in 4/4L+ lines). Therefore, we reported the real-world data of ALP+FUL efficacy in pts with HR+/HER2−ABC with PIK3CAm from initial year access in Russian Federation. Methods: Pts with HR+/HER2- ABC with PIK3CAm were treated with ALP 300mg QD orally and FUL 500mg IM until disease progression or intolerance. The primary endpoints were progression free survival (PFS) and clinical benefit (CB) defined per RECIST 1.1. Here we present the results of treatment pts with ALP+FUL in routine practice after prior FUL, chemotherapy and outcomes depend on the line of therapy in which pts received ALP+FUL. Results: 139 pts with HR+/HER2-ABC with PIK3CAm were included in our retrospective analysis from 2020 to 2023. Median lines of previous treatment in ABC was three (1-9), the most pts have received CDK 4/6, n=123 (86%), fulvestrant-containing regimens, n=83 (79%) and CT, n=77 (55%). The median of PFS (mPFS) on ALP+FUL was 7.0 months (CI 95%: 5.0-8.9); CB was achieved in 58% of pts, including partial response in 18% and stable disease ≥6 months in 40% pts. The mPFS was statistically longer in pts who didn't receive CT and FUL compared with pts who had prior CT and FUL-containing regimens (Table). Pts received AlP+FUL in the 2L (n=45, 32%), 3L (n=35, 25%), 4L and 4L+ (n=59, 42%). The mPFS was statistically longer in pts treated with ALP+FUL in earlier lines (Table 1). The pts received metformin for hyperglycemia (HG) prevention according to their metabolic status; any grade of hyperglycemia (HG) was reported in 86 out of 138 pts (62%). HG grade (G) 1 was detected in 43 (31%) pts, G2 – in 27 (20%) pts, G3 – in 16 (12%) pts and no cases HG G4 were detected. 14 patient required ALP dose reductions to 250 mg due to HG G3; 3 pts discontinued ALP due to HG. Other most common AEs included rash and creatinine increase. The pts received cetirizine 10 mg orally during 4 weeks for rash prevention; rash any G occurred in 53 (39%) pts (G1 - 7%, G2 -10% G3 -19%, G4 - 0,7%), 20 pts required ALP dose reductions to 250 mg due to rash G3 and 11 pts discontinued ALP due to AEs. Blood creatinine increase was detected in 21/139 – all G 1-2. Conclusions: ALP+FUL demonstrated high efficacy in heavily pretreated pts with HR+/HER2- ABC with PIK3CAm in routine practice. ALP+FUL should be used in earlier lines of treatment in metastatic setting before chemotherapy and/or fulvestrant-containing regimens. [Table: see text]