Background: CDK4/6i improve survival outcomes for first-line treatment of patients with hormone receptor positive (HR+), human epidermal growth factor-2 negative (HER2-) MBC. Yet, not all eligible patients (pts) receive a first-line CDK4/6i. We sought to describe factors associated with not receiving a first-line CDK 4/6i among MBC pts treated at our institution. Methods: Retrospective cohort of pts with HR+, HER2- MBC diagnosed between May 1, 2015 and June 30, 2019 treated at Johns Hopkins clinic sites in Baltimore City (BCi), Baltimore County (BCo), and Washington DC (DC). Primary outcome was receipt of a first-line CDK 4/6i. Clinical and demographic factors were abstracted from the electronic medical record. Patient zip-code was used to define a low-income neighborhood (LIN) as an area where >10% of households have median income below the federal poverty level. Univariate and multivariable logistic regression models (determined using a stepwise model selection approach) were performed to identify factors associated with not receiving a first-line CDK 4/6i. Results: Of the 211 pts in the cohort, 203 (96.2%) were female, 133 (63%) were White, and 53 (25%) were Black. Median age was 58 yrs (range 25-90 yrs). 26% of pts had de novo MBC and 44% had visceral disease at diagnosis. About half, 104 (49%), were privately insured, 83 (49%) had Medicare, and 15 (7.1%) had managed care plans including Medicaid. 118 (56%), 43 (20%), and 50 (24%) pts were treated in BCi, BCo, and DC respectively. 60% (n=126) of pts received a first-line CDK 4/6i and there was a trend of increased utilization over time with 39% of pts receiving first-line CDK4/6i in 2015 and 67% in 2019. On univariate analysis, LIN, clinic site, and year of MBC diagnosis (2015-2017 vs 2018-2019) were associated with first-line CDK4/6i use. The multivariable model included age, race, clinic site, LIN, and year of MBC diagnosis. In this model, pts treated in BCi were 58% less likely to receive first-line CDK 4/6i compared to those treated in BCo (OR 0.42, 95% CI 0.18-0.95). Those diagnosed with MBC in 2017 or later were 2.6 times more likely to receive first-line CDK4/6i than those diagnosed prior (OR 2.63, 95% CI 1.45-4.83). Those who lived in a LIN were 39% less likely to receive first-line CDK4/6i vs those in a non-LIN, though this was no longer statistically significant (OR 0.61, 95% CI 0.32-1.13). Conclusions: We identified disparities in the use of CDK4/6i for first-line treatment of MBC. Lower use was observed among pts who received care at our urban Baltimore city site with a trend towards lower use among pts from lower-income neighborhoods. These findings highlight potential barriers with accessing oral cancer therapies - cost, patient distrust, and/or systemic bias. Further work is needed to delineate the multi-level factors contributing to these disparities and to develop resources to overcome these barriers and achieve equitable utilization of these drugs.