Multicenter phase 2 trial of metformin for prevention of alpelisib-related hyperglycemia in HR+/HER2-/PIK3CA-mutated advanced breast cancer

Hyperglycemia is an early and frequent adverse event during alpelisib treatment. The multicenter phase 2 METALLICA trial in Spain evaluated prophylactic metformin before the start of alpelisib and endocrine therapy for HR+/HER2-/PIK3CA mutated advanced breast cancer (aBC). During the first eight weeks of treatment, grade 3 or 4 hyperglycemia was seen in one patient (2.1%) with baseline normal glucose and HbA1c, and in 15% of patients with baseline prediabetes. Serious treatment-related adverse events occurred in 10.3%. Discontinuation of alpelisib because of AEs was reported in 13.2%, none caused by hyperglycemia. The median progression-free survival was 7.3 months (95% CI 5.9-NR), the objective response rate was 20.6% (11.7-32.1), and the clinical benefit rate was 52.9% (40.4-65.2). The authors conclude that in HR+/HER2-/PIK3CA-mutated aBC, prophylactic metformin before alpelisib plus endocrine therapy resulted in low incidence of alpelisib-induced hyperglycemia.