Abstract PS1-12-28: Real-world outcomes of first line palbociclib combined with endocrine treatment in HR+/HER2- metastatic breast cancer: 5-year data from the French ESME cohort

Abstract Background: CDK4/6 inhibitors (CDK4/6i) are the standard of carein first line (1L) treatment for HR+/HER2- metastatic breast cancer (MBC) patients.This study aimed to characterize patient profiles and outcomes in the FrenchESME real-world (RW) cohort for patients in academic centers receiving 1L palbociclibcombined with endocrine therapy (ET). Material and Methods: The ESME MBC cohort is a nationalregistry collecting individual-level patient data from 18 French ComprehensiveCancer Centers (NCT03275311). This analysis included all patients aged ≥18years with newly diagnosed HR+/HER2- MBC who initiated in 1L palbociclib within90 days after ET initiation, between January 2018 and December 2023 outsidea clinical trial. Overall survival (OS) and time to next treatment(TTNT) were assessed using Kaplan-Meier estimations. Multivariable modelling(Cox-regression) was undertaken to identify independent prognostic factors forthese endpoints. Results: Among 3,587patients treated in 1L by CDK4/6i combined with ET for HR+/HER2- MBC, 2,267 patientsinitiated palbociclib, including 340 (15.1%) premenopausal women and 7 (0.3%)men. Median age at MBC diagnosis was 69 years (range 29-95). Visceralmetastases were present in 38.0% of cases, 37.8% of patients had bone-onlydisease, and 53.1%, 22.5% and 24.4% of patients presented 1, 2 and ≥3 metastaticsites, respectively. De novo MBC accounted for 33.1% of patients. Forrelapsed MBC, treatment-free intervals (TFI) were ≤12 months in 22.5% and 12months in 31.7% of the whole population (missing data in 12.7%). Palbociclibwas combined with an aromatase inhibitor (AI) in 1,651 (72.8%) patients, mostlyin ET-sensitive disease (1,297/1,651 of de novo or TFI 12 months) andwith fulvestrant in 449 (19.8%) patients, mainly for ET-resistant disease (323/449of TFI ≤12 months). Atthe time of the data cut-off, the median follow-up was 54.9 months 95% CI 52.9-56.8;median OS was 49.9 months 47.4-52.3 and median TTNT was 21.3 months 19.8-22.3in the overall population. These results varied by different subgroups (table1). Interestingly, multivariable Cox models showed age and TFI (and not ETpartner) as only independent prognostic factors for OS. Additional analysesaccording to the double stratification ET partner and endocrine sensitivitywill be presented at the conference. Conclusions: In this academic treatment setting, HR+/HER2- patientstreated with palbociclib + ET demonstrate similar outcomes overall and across subgroupfor TTNT and OS as seen in other RW and randomized studies. These results underscorethe impact of some characteristics on effectiveness outcomes, i.e. age, numberof metastatic sites, type of disease and TFI. Citation Format: T. Grinda, S. Eltaief, E. Brain, T. Bachelot, V. Diéras, F. Dalenc, V. Massard, M. Decrop, A. Coumert, M. Arnedos, A. Mailliez, M. Carton, L. Bosquet, J. Frenel, W. Jacot. Real-world outcomes of first line palbociclib combined with endocrine treatment in HR+/HER2- metastatic breast cancer: 5-year data from the French ESME cohort 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 PS1-12-28.