Impact of GLP-1 receptor agonists in hormone receptor–positive breast cancer patients receiving CDK4/6 inhibitors.

1100 Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes and obesity due to their efficacy in weight reduction and glycemic control. Beyond their metabolic benefits, GLP-1 RAs delay gastric emptying, which may affect the absorption of oral medications like cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i). Additionally, CDK4/6i and GLP-1 RAs share overlapping gastrointestinal (GI) toxicities such as diarrhea and nausea, which could impact medication tolerability and clinical outcomes. This investigation aimed to characterize the safety of concomitant GLP-1 RA and CDK4/6i use in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods: We performed a single-center, retrospective chart review evaluating adult patients prescribed a CDK4/6i for HR+ breast cancer at Winship Cancer Institute between October 2022 and May 2025. Patients receiving concomitant GLP-1 RA and CDK4/6i (Group 1) were matched 1:1 to patients receiving a CDK4/6i without GLP1-RA (Group 2). Matching criteria included prescribed CDK4/6i, treatment indication (adjuvant or metastatic), age (≥65 years, 45-64 years, and <45 years), and race. The primary outcome was safety, assessed by adverse drug reactions, dose reductions, and discontinuations. Results: 82 patients were reviewed, median age 54 years old. Half (41 patients, 50%) were prescribed abemaciclib, 21 (25.61%) palbociclib, and 20 (24.39%) ribociclib. 41 patients receiving concomitant GLP-1 RA and CDK4/6i (Group 1) were matched to 41 patients receiving a CDK4/6i without GLP1-RA (Group 2). Of those in Group 1, 20 were prescribed a GLP-1 RA for diabetes and 18 for obesity. Median BMI was 32.76 kg/m2 (range, 28.44-36.28 kg/m2) in Group 1 compared to 26.32 kg/m2 (range, 23.74-28.05 kg/m2) in Group 2. Semaglutide and tirzepatide were the most prescribed GLP-1 RAs. 38 patients (51.35%) in Group 2 experienced an ADR associated with CDK4/6i compared to 36 patients (48.65%) in Group 1 (p-value, 0.457). Median time to first documented ADR was 14 days (range, 8-21 days) in Group 2 compared to 18 days (range, 11-36 days) in Group 1 (p-value, 0.086). 24 patients (55.81%) in Group 1 experienced a GI ADR compared to 19 patients (44.19%) in Group 2 (p-value, 0.269). Conclusions: Patients receiving CDK4/6i without GLP-1 RA experienced earlier onset and a numerically higher incidence of ADRs compared with those receiving concomitant GLP-1 RA and CDK4/6i therapy, though differences did not reach statistical significance. Ongoing analyses of treatment adherence and progression-free survival will be reported out at a later date. Larger, multi-center studies are warranted to further characterize safety and potential pharmacologic interactions between GLP-1 RAs and CDK4/6i.