Real-World Study Reveals Lower Hyperglycemia Management Burden with Capivasertib Versus Alpelisib in Metastatic Breast Cancer
核心洞察
A retrospective analysis of 555 patients with HR-positive/HER2-negative metastatic breast cancer (搜索) found that capivasertib required significantly less antihyperglycemic medication management compared to alpelisib.
Patients treated with capivasertib showed lower rates of antihyperglycemic agent use during treatment (28.2% vs 48.6%) and smaller increases from baseline (+8.0% vs +23.6%) compared to alpelisib.
Among patients without baseline diabetes, 19.0% of capivasertib-treated patients required antihyperglycemic agents versus 39.3% of alpelisib-treated patients.
A new real-world study analyzing claims data from 555 patients with hormone receptor-positive/HER2-negative metastatic breast cancer (搜索) reveals significant differences in hyperglycemia (搜索) management requirements between two PI3K/AKT pathway (搜索) inhibitors. The retrospective analysis found that patients treated with capivasertib required substantially less pharmacological management of hyperglycemia compared to those receiving alpelisib.
Study Design and Patient Population
The retrospective, observational cohort study analyzed claims data from the Komodo Research Dataset, examining adult patients with metastatic breast cancer (搜索) who initiated capivasertib or alpelisib on or after November 16, 2023. The study included 411 capivasertib-treated patients with a median follow-up of 6 months and 144 alpelisib-treated patients with a median follow-up of 7 months.
Baseline characteristics were comparable between the two cohorts, with mean ages of 61.7 years versus 61.8 years, White race representation of 58.4% versus 54.2%, and diabetes mellitus (搜索) prevalence of 18.7% versus 21.5% for capivasertib and alpelisib groups, respectively.
Differential Hyperglycemia Management Requirements
The analysis revealed striking differences in antihyperglycemic medication use between the two treatment groups. During treatment, a significantly lower proportion of patients on capivasertib used antihyperglycemic agents compared to those receiving alpelisib (28.2% vs 48.6%). Insulin use specifically was also markedly lower with capivasertib (6.8% vs 16.0%).
Relative to baseline, the increase in antihyperglycemic use was substantially smaller with capivasertib versus alpelisib for any agent (+8.0% vs +23.6%) and for insulin specifically (+1.7% vs +12.5%). Similar patterns were observed across metformin and other oral antihyperglycemic drug classes.
Impact on Patients Without Baseline Diabetes
Among patients without baseline diabetes mellitus (搜索), the differences were particularly pronounced. Only 19.0% of capivasertib-treated patients required any antihyperglycemic agent during treatment, compared to 39.3% of alpelisib-treated patients. For patients without baseline antihyperglycemic use, initiation of these medications during treatment occurred less frequently with capivasertib versus alpelisib (13.7% vs 35.2% for any agent; 2.8% vs 13.7% for insulin).
Clinical Trial Context
The real-world findings align with differences observed in clinical trials using different CTCAE versions. The SOLAR-1 trial reported hyperglycemia (搜索) rates of 63.7% overall (grades 3-4, 36.6%) with alpelisib plus fulvestrant, while the CAPItello-291 trial showed 16.3% overall (grades 3-4, 2.3%) with capivasertib plus fulvestrant.
Treatment Duration Considerations
The study also revealed differences in treatment duration, with only 3.5% of capivasertib patients remaining on treatment for more than 90 days compared with 39.6% for alpelisib patients. This difference in treatment persistence may reflect varying tolerability profiles between the two agents.
Clinical Implications
The researchers concluded that this real-world descriptive analysis suggests patients treated with capivasertib required less pharmacological management of hyperglycemia (搜索) than those treated with alpelisib. These findings highlight the differential risk of hyperglycemia across PI3K/AKT pathway (搜索) inhibitors and may inform clinical decision-making for treatment selection in HR-positive/HER2-negative metastatic breast cancer (搜索).
The study provides valuable real-world evidence to complement clinical trial data, offering insights into the practical management challenges associated with different PI3K/AKT pathway (搜索) inhibitors in routine clinical practice.