Abstract PS1-11-01: Impact of prior CDK 4/6 inhibitor treatment on the efficacy of everolimus and exemestane or fulvestrant in hormone receptor positive HER 2 negative (HR+/HER2-) metastatic breast cancer (MBC): a restrospective analysis of 144 patie

Abstract INTRODUCTION HR+/HER2- MBC remains one of the leading causes of cancer related mortality in woman worldwide. Standard treatment includes endocrine therapy and targeted agents such as everolimus, an mTOR inhibitor. The impact of prior CKD4/6 inhibitor treatment on the efficacy of everolimus is not well defined. This study evaluates the effect of prior CDK4/6 exposure on survival outcomes in HR+HER2- MBC treated with this combination. OBJETIVES To compare progression-free survival (PFS) and overall survival (OS) according to prior CKD4/6 inhibitor exposure in patients treated with everolimus and exemestane or fulvestrant. METHODS Retrospective analysis of 144 women with HR+/HER2- MBC treated with the combination of everolimus plus exemestane or fulvestrant between October 2010 and October 2023. Two cohorts were compared: cohort 1 without previos CDK 4/6 inhibitor and cohort 2 with previous CKD4/6 inhibitor (palbociclib or ribociclib). The analysis was conducted on June 2025. RESULTS A total of 144 women were included. The median follow up was 31.3 month (2.23-103). 11 patient were on treatment on the time of analysis. Table 1 highlights baseline characteristic. Median PFS was 7.4 months in the overall population, 8.2 month in cohort 1 and 6.1 months in cohort 2. The adjusted HR for previous treatment lines was 1.14 for previous CKD4/6 treatment (p 0.474). The HR for progression in patient with previous CDK 4/6 was 1.7 (p=0.119) independent of previous line duration. Median OS from the start of everolimus was 37 months in the overall population, 40.7 month in cohort 1 and 35.9 months in cohort 2. The adjusted HR for previous treatment lines was 1.1 (p= 0.6) for previous CKD4/6 treatment. Everolimus was discontinued due to toxicity in 27% of patients; 33% required dose reduction. Main toxicitys included mucositis (44& any grade), pneumonitis( >G2 17%) and hyperglycemia (>G2 3%). CONCLUSION To our knowledge, this is the second largest reported series to date supporting the prior hypothesis that prior CDK4/6 inhibitor treatment is associated with shorter PFS and OS in HR+/HER2- MBC patients treated with everolimus and exemestane. These findings highlight the need to optimize post CDK4/6 treatment strategies. BIBLIOGRAPHY 1. Baselga J et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9.2.Mo H et al. Real-World Outcomes of Everolimus and Exemestane for the Treatment of Metastatic Hormone Receptor-Positive Breast Cancer in Patients Previously Treated With CDK4/6 Inhibitors. Clin Breast Cancer. 2022 Feb;22(2):143-148. Citation Format: M. Otaño, A. Paisan, C. Fernandez, A. Lahuerta, N. Ancizar, A. Urruticoechea, I. Alvarez Lopez. Impact of prior CDK 4/6 inhibitor treatment on the efficacy of everolimus and exemestane or fulvestrant in hormone receptor positive HER 2 negative (HR+/HER2-) metastatic breast cancer (MBC): a restrospective analysis of 144 patients [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 PS1-11-01.