Abstract PS5-04-08: Abemaciclib plus endocrine therapy in HR+/HER2- advanced breast cancer: insights from an Italian retrospective observational study

Abstract Rationale: Abemaciclib, approved in Italy since January 2020, improves progression-free survival (PFS) and overall survival (OS) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC). This retrospective study described the demographic and clinical characteristics of patient with ABC treated with abemaciclib plus endocrine therapy (ET) and evaluated its effectiveness in routine clinical practice in Italy. Methods: This is an Italian, multicenter, retrospective study. Data on patients with HR+/HER2− ABC who started abemaciclib between Jun-21 and Jun-22 was collected from 13 sites. The study period spanned from initial diagnosis to 24 months post-abemaciclib initiation. The primary endpoint, 24-month PFS in real-world (rwPFS) including the rwPFS rate, was estimated using the Kaplan-Meier method. Co-primary endpoints include overall response rate (rwORR), clinical benefit rate (rwCBR), time to treatment discontinuation (rwTDT). Results: 199 patients, who started abemaciclib in combination with fulvestrant or an aromatase inhibitor (AI), were enrolled. At abemaciclib initiation, the mean age was 62 years, and most patients (97.5%) had an ECOG PS of 0-1. Endocrine resistant (ER) disease was observed in 44.2% of patients; the remaining 55.8% were endocrine-sensitive (ES), including 60 patients with de novo metastatic disease. The most frequent sites of metastasis were bone (61.8%) and visceral tissues (45.2%), with the liver being the most affected organ (51.1%). Brain metastases accounted for 4%. Abemaciclib was primarily administered as first line (88.4%) or second line (10%) therapy. The most common combination agent was fulvestrant (51.3%), mainly in ER or subsequent lines, followed by letrozole (45.7%), among AIs. The median rwPFS in the overall population was 22.2 months (95% CI: 19.2-25.3) and 18.3 (95% CI: 14.9-22.5) and 26.3 (95% CI: 22.9-29.8) months for ER and ES, respectively. rwPFS rate at 24 months was 45.7% (overall), 34.0% (ER), and 61.2% (ES), respectively. The rwORR was 46.1% (95% CI: 38.6-53.7), with rwCBR of 68.5% (95% CI: 61.2-75.3). Abemaciclib was initiated at 150 mg BID in 92.5% of cases. Dose modifications occurred in 60.8% of patients, and 53.2% (n=106) required dose reductions. Patients who reduced their dose had a longer rwPFS of 26.3 (95% CI: 21.6-31.0) months. Proper management supports staying on treatment and leads to improved outcomes. Approximately 58.3% (n=116) permanently discontinued abemaciclib during the observation period, while 41.7% (n=83) remained on treatment at final observation (24 months). Among those who discontinued abemaciclib, 67.2% stopped the combination agent simultaneously. Most discontinuations were due to disease progression (37.7%), with AEs accounting for 12.6%. Notably, following dose reduction, only 8% of patients discontinued treatment due to AEs. The median rwTDT was 21.2 months (95% CI: 17.2-25.2). Conclusion: These real-word results are consistent with those from the MONARCH 2 and MONARCH 3 trials, confirming the effectiveness of abemaciclib in combination with ET for patients with HR+/HER2− ABC, across ER and ES settings. Two years after treatment initiation, 45.7% of patients remained progression-free and 41.7% continued therapy, indicating that abemaciclib is an effective and manageable therapeutic option for patients with ABC. Patients who reduced their dose had a numerically longer rwPFS, reinforcing the importance of appropriate use of patient management strategies to improve abemaciclib treatment persistence and clinical outcomes. Citation Format: E. Munzone, V. Guarneri, A. Ferro, A. Beano, G. V. Bianchi, A. Fabi, G. Bianchini, F. Riccardi, F. Giovanardi, V. E. Chiuri, E. Fiorio, I. Portarena, P. Tassone, A. Avitabile, S. Baffini, M. A. Sarno, A. Tamma. Abemaciclib plus endocrine therapy in HR+/HER2- advanced breast cancer: insights from an Italian retrospective observational study [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 PS5-04-08.