Endocrine Abstracts

Background: Alpelisib is an α-selective PI3K inhibitor indicated for the treatment of postmenopausal women and men with hormone receptor-positive (HR+), human epidermal growth receptor 2-negative (HER2–), PIK3CA-mutated locally advanced or metastatic breast cancer following disease progression or after endocrine therapy. Hyperglycemia is the most common adverse event (up to 60%) associated with its use. It occurs more frequently and lasts longer in patients with prediabetes or type 2 diabetes (DM2) at baseline. 4 grades of Alpelisib-induced hyperglycemia are defined by the FDA. In grades 3 (>13.9–27.8 mmol/l) and 4 (>27.8 mmol/l), current guidelines recommend to interrupt or even discontinuate Alpelisib.

Case report: We present the case of a 58-year-old woman with a history of hypertension, dyslipidemia, obesity, and untreated type-2 diabetes. In 2010, she received surgery for breast cancer (HER2+, HR+, PIK3CA-mutated). Since 2018, lymph node and bone progression were discovered despite hormonal treatment and radiotherapy for symptomatic control. She started treatment with Alpelisib-Fulvestrant in July 2022, with grade 3–4 hyperglycemia (9–15 mmol/l) appearing after a week. She was referred to an Endocrinologist and began treatment with a low-carbohydrate diet, metformin titrated to a maximum dose of 1000 mg twice a day, linagliptin 5 mg once a day and insulin therapy in a basal-bolus regime at 0.2 IU/kg (Table 1). Despite this treatment, in the following months both fasting and postprandial blood glucose levels remained between 10 and 15 mmol/l, so it was necessary to increase the insulin dose progressively. In November 2022, high blood glucose levels persisted, with the control CT scan showing stable disease. She continued Alpelisib and kept increasing insulin dose up to 0.95 IU/kg. In January 2023, glycemic targets were achieved (preprandial 5–6.66 mmol/l, postprandial 5.55–9.99 mmol/l, HbA1c of 7.3%) and dose was even lowered up to 0.7 IU/kg to prevent fasting hypoglycemia.

Conclusion: Grade 3–4 AIH management with low CH diet, metformin, linagliptin and basal-bolus insulin therapy at high doses has allowed our patient to accomplish hyperglycemia control after 6 months of treatment, without interrupting Alpelisib while achieving stable oncological disease to date.