Abstract Background: NCCN recommends the combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) as the standard first line treatment in ER+/HER2- metastatic breast cancer (MBC). Despite CDK4/6i demonstrating significant progression-free survival in clinical trials, real-world adherence to this combination remains inconsistent. We characterize the factors that influenced the adherence to combination therapy in patients with ER+/HER2- MBC. Methods: We conducted a multi-center retrospective review of electronic health records of patients with ER+/HER2- MBC between years 2015 - 2022 and imputed data into a standardized REDCap database. Bivariate group comparisons were performed using chi-squared or ANOVA, as appropriate. Multivariate logistic regression was done to identify independent factors associated with adherence to combination therapy. Statistical analyses were performed using R. A p-value 0.05 was considered statistically significant. Results: 152 women with a median age of 64 years (IQR: 52.3-73.8) were included. 27.6% were Black/African American and 44.7% were White. The most prescribed CDK4/6i was palbociclib (65.2%), then abemaciclib (25.9%). ECOG performance status was 2 in 49.3% of cases. 79.6% of patients had fewer than three metastatic sites. Adherence to combination therapy was seen in 112 patients (73.7%). Of the 40 patients who did not receive CDK4/6i, 75% had justification, mostly due to insurance (23.3%), patient preference (23.3%) and comorbidities (20%). No significant differences in combination therapy across race or ethnicity were found. Insurance influenced the type of CDK4/6i prescribed, with palbociclib being most frequently used among patients with mixed (61.9%), public (50.6%), and private (39.4%) insurance (p = 0.011). The multivariate analysis showed that patients with fewer than three metastatic sites were more likely to receive combination therapy (77.7%) vs those with three or more sites (58.1%), p = 0.027; OR= 3.41 (95% CI: 1.19-9.72), p= 0.022, independent of other variables analyzed. Conclusions: Patient with low burden disease ( 3 metastatic sites) were more likely to receive combination therapy with CDK4/6i and ET. These findings may be driven by the preferred use of chemotherapy in high burden disease/visceral crises as these patients were excluded from trials such as PALOMA-2 due to the need for rapid disease control. Citation Format: M. C. Anyanwu, N. Wagner, H. Becerra, W. Siddiqui, I. Yao, J. Catlett, O. Tracy, T. K. Esantsi, M. Kier. Institutional adherence to CDK4/6 inhibitor use in ER+/HER2- metastatic breast cancer: A retrospective cohort 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 PS1-12-25.
Anyanwu et al. (Tue,) studied this question.