Abstract PS3-09-18: Early AB-ITALY: Evaluating Real-World Use of Adjuvant Abemaciclib and Drug Interaction Risk in HR+/HER2- early Breast Cancer

Abstract Introduction Abemaciclib is a selective CDK4/6 inhibitor approved for adjuvant treatment in patients with high-risk hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer (eBC). The MONARCH-E trial demonstrated significant increase in invasive disease-free survival (iDFS) when combined abemaciclib with endocrine therapy. Nonetheless, real-world data regarding safety, treatment adherence, and drug-drug interactions (DDIs), particularly among elderly and comorbid populations often excluded from clinical trials, remain limited. Evaluating these real-world factors is critical to optimizing treatment and patient outcomes in clinical practice. Methods This retrospective study analyzed consecutive patients with HR+/HER2- eBC treated at 21 Italian oncology centers who received adjuvant abemaciclib combined with an aromatase inhibitor (AI). Comprehensive clinical data, medication usage, and adverse events (AEs) were collected. Drug-PIN®, a platform integrating clinical (age, sex, race, smoking and alcohol habits), laboratory (renal and hepatic function), and pharmacological parameters (chronic concomitant treatments), was utilized to assess DDIs, providing a numeric interaction score (Drug-PIN score) and qualitative risk tiers (green: none; yellow/dark yellow: intermediate; red: high risk). Statistical analyses, including univariate and multivariate approaches, identified predictors of AEs. Results We enrolled 714 patients with a median age of 56 years (range 30-86); 44% were premenopausal, and 51% had at least one comorbidity, while 13% had multiple comorbidities. Notably, 60 patients (8.4%) were aged ≥75 years. Genetic testing performed in 350 patients identified 29 mutated. Disease characteristics included node-positive (c/pN2) status in 389 (54%), carcinoma of no special type in 73%, lobular carcinoma in 14%, and high-grade tumors (G3) in 57%. Chemotherapy was omitted in 10% of cases. Oncotype DX testing was conducted in 42 patients (6%), with a mean recurrence score (RS) of 26 (range 8-50); 20 had an RS ≤25. With a median follow-up of 13.2 months (range 1-33), 85% of patients experienced any-grade AEs, primarily diarrhea (76%), asthenia (41%), and neutropenia (27%). Grade ≥3 AEs occurred in 30%, with severe diarrhea reported in 11%, mostly during the first two cycles. Dose reductions were required in 47% and discontinuation due to toxicity occurred in 9.5%. Patients aged ≥75 showed comparable diarrhea rates (p = 0.20) but a trend toward increased dose reductions (p = 0.09). Concomitant medications were reported in 50% of patients, and 8% had polypharmacy. The median Drug-PIN interaction score was 12.0 (range 3-100), with at least one DDI identified in 17.3% of the patients, with 10.5% categorized in the intermediate-high or high-risk tiers. Notably, high-risk DDIs occurred more frequently among patients who discontinued treatment due to toxicity (25% vs 10%, p = 0.04). Conclusions Adjuvant abemaciclib is safe and manageable in real-world settings, even among elderly and comorbid patients, showing slightly higher but comparable AE rates and dose adjustments relative to clinical trials. Overall, abemaciclib treatment presents a low incidence of drug-drug interactions. However, the significant association observed between DDIs and dose reductions emphasizes the necessity for further prospective investigations to better define these interactions and inform clinical practice. Citation Format: S. Scagnoli, M. Verrico, S. Pisegna, R. Caputo, F. Pantano, P. Falbo, G. D'Auria, A. Orlandi, D. Alesini, I. Portarena, P. Vici, M. Fabbri, L. Rossi, T. Di Palma, G. Gentile, M. Bonomo, L. Sisca, C. Bonadonna, L. Strigari, G. Ricciardi, M. Pizzoli, E. Giordani, A. Irelli, M. Sanò, M. Palleschi, R. Preissner, A. Daneri, O. Garrone, G. Bianchini, C. Martinelli, C. Criscitiello, M. Lambertini, A. Fabi, M. De Laurentiis, L. Del Mastro, G. Curigliano, P. Marchetti, A. Botticelli. Early AB-ITALY: Evaluating Real-World Use of Adjuvant Abemaciclib and Drug Interaction Risk in HR+/HER2- early Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-09-18.