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William J. Gradishar, MD, FACP, FASCO


How Common Is Alpelisib-Induced Hyperglycemia in Metastatic Breast Cancer?

By: Amanda E. Ruffino, BA
Posted: Wednesday, January 31, 2024

The use of alpelisib has improved progression-free survival when combined with the estrogen receptor antagonist fulvestrant in metastatic hormone receptor–positive, PIK3CA-mutant breast cancer. Published in the journal Cancer, a retrospective study focused on 247 patients receiving alpelisib between 2013 and 2021, aiming to understand the incidence, risk factors, and management of alpelisib-associated hyperglycemia. Neil M. Iyengar, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues reported a significant association between hyperglycemia and nonclinical trial treatment, emphasizing the need for careful glycemic control before initiating this kinase inhibitor in standard-care settings.

Among patients, 61.5% developed any-grade hyperglycemia, with 29.2% experiencing grade 3 or 4 hyperglycemia within a median onset of 16 days. Of note, 40.5% received alpelisib in clinical trials, showing significantly lower hyperglycemia rates compared with standard care (any-grade, 34.0%; grade 3 or 4, 13.0%; P < .001). Baseline hemoglobin A1c (HbA1c) was identified as a significant factor, correlating with hyperglycemia development (P < .001) and alpelisib dose adjustment (P = .015).

Among those with hyperglycemia, 40.9% received treatment, predominantly with metformin. A total of 19.8% were referred to an endocrinologist, and such referrals correlated with prescriptions of an SGLT2 (sodium-glucose transport protein 2) inhibitor (P = .007). These findings underscore the importance of comprehensive management in this patient population.

The investigators emphasized the considerable difference in hyperglycemia rates between alpelisib treatment in standard care and on clinical trials. Baseline HbA1c is identified as a predictor for hyperglycemia and subsequent dose adjustments, emphasizing the importance of optimizing glycemic control before initiation of alpelisib. The underuse of endocrinologist referrals suggests the need for a more proactive approach to ensure optimal patient outcomes during alpelisib treatment.

Disclosures: For the study authors’ full disclosures, visit

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