The association between baseline patient characteristics and alpelisib-induced hyperglycaemia in patients with HR+, HER2-, PIK3CA-mutated metastatic breast cancer.

Abstract

e13059 Background: Alpelisib (A) is a PI3Kα-selective inhibitor and degrader which, in combination with fulvestrant, has been approved for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC). Hyperglycemia is the most commonly observed adverse event of A. A pooled analysis of X2101 AND SOLAR-1 trials showed the association between five baseline patient characteristics (age, fasting plasma glucose (FPG), glycated haemoglobin, body mass index (BMI) and blood monocyte count (BMC)) and the development of A-induced hyperglycaemia (HG). We examined the association between baseline factors and the A-induced HG grade (G) ≥2 in a real-world setting. Methods: We performed the retrospective observational study and included patients (pts) with HR+, HER2-, PIK3CA-mutated metastatic breast cancer who received A + fulvestrant between Oct 18, 2019, and Oct 13, 2022, at the Institute of Oncology Ljubljana. Electronic records were reviewed. Baseline age, FPG, glycated haemoglobin, BMI and BMC before the start of A therapy and glucose levels during treatment with A were collected. Random plasma glucose values (RPG) were used for HG grading according to CTCAE V. The chi-square test was used to determine the association between the baseline characteristics and A-induced HG G ≥2. Results: Thirty-one female pts were included in the analysis. The median follow-up was 21 months, and the median duration of A treatment was 5.4 months. The baseline pts characteristics were as follows: median age 58 years (range 33–80), median FPG 5.6 mmol/L (range 3.10–8.6), median BMI 21.7 kg/m² (range 18.7–30.4), and median BMC was 10.3% (range 5.3–16.6). Baseline glycated haemoglobin values were only known for 58.1% of patients, so we did not further analyse them. The highest HG grades during treatment with A were as follows: G0 in 14 pts (45.2%), G1 in 5 pts (16.1%), G2 in 6 pts (19.4%), G3 in 6 pts (19.4 %). The calculated cut-off values associated with A-induced HG ≥2 were: age above 65 years, FPG above 5.9 mmol/L and BMC more than 11.5. None of the BMI cut-off values was associated with HG G≥2. Association between the baseline age, FPG and BMC and A-induced HG G≥2. Conclusions: Age over 65 years, FPG more than 5.9 mmol/L and BMC more than 11.5% have a statistically significant higher probability for A-induced HG G≥2. Therefore, these patients need more frequent blood glucose measurements, lifestyle adjustments and early treatment with metformin and/or other oral glucose-lowering agents. [Table: see text]