Abstract Background: CDK4/6 inhibitors are a standard first-line treatment for HR+/HER2− metastatic breast cancer (MBC). However, real-world data are needed to confirm their effectiveness outside clinical trial settings. This study evaluates progression-free survival (PFS) and identifies predictors of early progression in patients who received first-line CDK4/6 inhibitors at a tertiary cancer center. Methods: We conducted a retrospective analysis of 82 patients with HR+/HER2− MBC treated at King Fahad Medical City, Riyadh, between January 2021 and December 2023. Patients were categorized based on receipt of first-line CDK4/6 inhibitors (n=59) vs non-CDK therapies (n=22). PFS was estimated using Kaplan-Meier methods. Subgroup analyses and logistic regression were performed to identify predictors of short PFS (12 months) among CDK4/6-treated patients. Results: Among the 82 patients, median age was 50 years (range: 30-78), 93% were female, 70% had de novo MBC, and 44% had visceral metastases. Visceral crisis was observed in 7.3% of the cohort.Of the 59 patients treated with first-line CDK4/6 inhibitors (33 palbociclib, 26 abemaciclib). Visceral metastases were present in 61%, while 32% had bone-only disease. AI was the endocrine partner in 71%, and fulvestrant in 29%. Median PFS was 22.2 months (range: 1.0-55.4), with longer PFS in de novo vs recurrent (24.3 vs 16.4 mo) and bone-only vs visceral metastases (27.9 vs 18.5 mo). No significant PFS difference was observed between palbociclib and abemaciclib.Multivariable analysis identified recurrent presentation and visceral metastases as predictors of shorter PFS. To date, death events occurred in only 11 of 82 patients (13.4%), precluding meaningful OS analysis. Conclusion: First-line CDK4/6 inhibitors offer substantial PFS benefit in HR+/HER2− MBC. No difference in outcome was observed between palbociclib and abemaciclib. OS data remain immature due to limited follow-up and low event rate. Recurrent presentation and visceral disease were associated with shorter PFS and may warrant closer monitoring in clinical practice. Citation Format: F. T. FAQIHI, M. F. ALDAWOUD, N. ALGAZLAN, A. A. ALMAZYAD, A. R. ALTAMIMI, M. RUDAINEE, M. M. ALHARBI, A. A. ALWOHAIBI, A. K. ALTWAIRGI. Real-world outcomes of first-line cdk4/6 inhibitor use in hr+/her2− metastatic breast cancer: a single-institution experience 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 PS1-12-30.
FAQIHI et al. (2026) studied this question.