Dynamics of hyperglycemia of patients treated with alpelisib: exploratory interim analysis of ITACA trial.

Abstract

Background: Alpelisib and fulvestrant combination has improved outcomes in patients with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-)- advanced breast cancer (BC) who relapsed or progressed on prior endocrine therapy. Hyperglycemia, on target toxicity, is a frequent adverse event occurring in over 60% of patients.

Objectives: The ITACA trial explores whether low carbohydrate dietary modifications and evening dosing of alpelisib to potentially mitigate impact of food on hyperglycemia. This exploratory interim analysis aimed to quantify the incidence and timing of hyperglycemia in the ITACA trial's pooled sample.

Methods: This exploratory interim analysis of the ongoing ITACA trial included 23 patients with HR+, HER2-negative metastatic BC receiving alpelisib and fulvestrant. The exploratory outcomes were grade 2-4 hyperglycemia-free survival and time to onset of hyperglycemia.

Results: Most patients, 21 (91.3%), experienced any-grade hyperglycemia (Grade 1: 9 [39.1%], Grade 2: 8 [34.8%], Grade 3: 4 [17.4%], and Grade 4: 0 [0.0%]) within the first week of alpelisib initiation. The median grade 2-4 hyperglycemia-free survival was 6 days (95% CI 3; 44 days).

Conclusions: This exploratory interim analysis demonstrated the rapid onset of hyperglycemia in patients receiving alpelisib, even with the ITACA trial's dietary interventions. Proactive monitoring, within the first week after initiation of treatment, and early management of hyperglycemia are crucial in this patient population.