140 Real-World Pharmacological Management of Hyperglycemia in HR-Positive/HER2-Negative Metastatic Breast Cancer Treated With Capivasertib or Alpelisib

Background

Hyperglycemia is an on-target, off-tumor effect of PI3K/AKT pathway inhibitors, including capivasertib and alpelisib, used in the treatment of hormone receptor–positive (HR+)/HER2-negative (HER2–) metastatic breast cancer. Clinical trials using different CTCAE versions have reported differing hyperglycemia rates –63.7% overall (grades 3-4, 36.6%) with alpelisib plus fulvestrant in SOLAR-1, and 16.3% overall (grades 3-4, 2.3%) with capivasertib plus fulvestrant in CAPItello-291, possibly leading to varying pharmacological burden for hyperglycemia management. This study describes the pharmacological management of hyperglycemia in patients treated with capivasertib or alpelisib in routine clinical practice.

Methods

This retrospective, observational cohort study analyzed claims data from the Komodo Research Dataset. The study population included adult patients with metastatic breast cancer who initiated capivasertib or alpelisib on or after November 16, 2023, had no prior PI3K or AKT inhibitor use, and no other primary cancer during the baseline period of 6 months prior to treatment start date (index treatment date). Included patients had continuous insurance enrolment of 3 months or more or until death if earlier. Descriptive analyses quantified antihyperglycemic treatments used during the baseline period and during the cancer treatment period, overall and stratified by baseline diabetes mellitus (DM) status.

Results

A total of 411 capivasertib-treated patients (median follow-up, 6 month; range, 0-17) and 144 alpelisib-treated patients (median follow-up, 7 month; range, 0-17) met inclusion criteria. Baseline characteristics were comparable between the 2 cohorts: mean age 61.7 years vs. 61.8 years; White race 58.4% vs 54.2%; DM 18.7% vs. 21.5%; and DM with complications 11.9% vs 12.5% (capivasertib vs alpelisib, respectively). A total of 3.5% of capivasertib patients were on treatment for more than 90 days compared with 39.6% for alpelisib. During treatment, a lower proportion of patients on capivasertib used antihyperglycemic agents than those receiving alpelisib (any agent 28.2% vs 48.6%; insulin 6.8% vs 16.0%). Relative to baseline, the increase in antihyperglycemic use was also smaller with capivasertib vs alpelisib (any agent +8.0% vs +23.6%; insulin +1.7% vs +12.5%) (Table). Similar patterns were observed for metformin and other oral antihyperglycemic classes. Among patients without baseline DM, the proportion receiving any antihyperglycemic agent during treatment was 19.0% (capivasertib) vs 39.3% (alpelisib). Among patients without baseline antihyperglycemic use, initiation of antihyperglycemic agent during treatment occurred less frequently with capivasertib vs alpelisib (any agent 13.7% vs 35.2%; insulin 2.8% vs 13.7%).

Conclusion

This real-world descriptive analysis suggests that patients treated with capivasertib required less pharmacological management of hyperglycemia than those treated with alpelisib. These findings highlight the differential risk of hyperglycemia across PI3K/AKT pathway inhibitors and may inform clinical decision-making for treatment selection in HR+/HER2– metastatic breast cancer.