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1049 Background: Hyperglycemia (HG) is an on-target effect of ALP, and prophylactic with metformin was shown to decrease the rate and severity of HG. Here we present efficacy and safety of ALP in a large cohort of patients with rational approach to metformin usage based on risk factors of HG. Methods: Patients (pts) with HR+/HER2- PIK3CAmut ABC were treated with ALP 300mg orally and FUL 500mg IM until disease progression or intolerance. The primary endpoints were progression free survival (PFS) and rate of grade 3/4 HG in different risk groups. Pts were stratified to risk groups of HG based on the algorithm (table 1) before starting ALP and received MET for prevention of HG. Results: A cohort comprised 139 pts, median lines of previous treatment in ABC was 3 (1-9): 88% received CDK4/6i, 60% - FUL, and 55% - chemotherapy (77) prior to ALP. The median PFS (mPFS) on ALP - was 7.0 (CI 95%: 5.0-8.9). The risk of HG was assessed in 138 pts: low (47), moderate (46), and high (42) risk, and 3 pts with type 2 diabetes mellitus. Any grade HG was reported in 62% pts, no cases HG G4 were detected. HG G3 was reported in 13% pts; 10% pts required ALP dose reduction to 250 mg due to HG G3; 3 pts (2%) discontinued ALP due to HG. The mPFS in our analysis was longer than in BYlieve trial in cohort C: 7.0 vs 5.6 mo. We suggest that prophylactic of HG allowed maintenance of full dose of ALP in most patients and thus increased the efficacy of ALP. Furthermore, in contrast to the METALLICA trial we distinguished a low risk group (33%) of pts who don’t need the prophylactic use of MET. Conclusions: Rational use of MET in pts with moderate and high risk of HG reduces the frequency and severity of HG, decreases the rate of ALP dose reductions and as a result may increase the efficacy of ALP. Pts with low risk of HG don’t need MET for HG prevention. Table: see text
Filonenko et al. (Wed,) studied this question.