BACKGROUND: As of June 2020, more than 2.5 million cases of COVID-19 and over 125,000 deaths related to COVID-19 have been confirmed in the United States (US). A strained healthcare system, quarantine orders, and national social distancing guidelines have forced healthcare providers to adopt new protocols to safely interact with and manage treatment for oncology patients. Recommendations put forth by the COVID-19 Pandemic Breast Cancer Consortium suggest some patients be considered for dose or schedule adjustments to ongoing treatment to reduce the risk of side effects and frequency of healthcare visits while deferring invasive procedures and initiating treatments with less need for monitoring or risk of side effects. The objective of this study was to understand whether patients with metastatic breast cancer (mBC) are experiencing changes in treatment during the pandemic in routine clinical practice in the US. METHODS: A retrospective cohort of patients, aged 18+ years, with a new mBC diagnosis receiving treatment between January 1, 2019, and April 30, 2020 was identified from the Flatiron longitudinal Cancer Database. The database comprises structured electronic health records from >280 cancer clinics and >800 sites of care, representing approximately 2.4 million US patients with cancer who are actively being treated for their disease. First-line treatments were assessed monthly for the study cohort and stratified by new and continuously treated patients in a given month. Types of first-line treatment included CDK4/6 regimen, endocrine monotherapy, chemotherapy, and other treatments (e.g., targeted monotherapy). Demographics, clinical characteristics, and treatment changes were descriptively summarized. RESULTS: 2680 patients with mBC were eligible for the analysis. The median age at metastatic diagnosis was 60 years, 99% were female, and 60% were White. Thirty-four percent had de novo metastatic disease at diagnosis and most received treatment at a community clinic. The most common breast cancer subtype was HR+/HER2- (66%). Between March and April 2020, the number of patients starting first-line therapy decreased 17% (from 121 to 100), whereas the number of continuing patients decreased 2% (from 837 to 817). The proportion of new starts receiving a CDK4/6 regimen averaged 35% between Jan 2019 and March 2020 with a decrease to 29% in April. The proportion of new starts receiving endocrine monotherapy was trending down from 37% in January 2019 to 22% in March 2020 (averaging 27% across this period); in April, the largest month to month change was observed in endocrine monotherapy use when the proportion of new patients increased to 28%. Treatment distributions appeared stable across the study months among continuing patients (Table 1). CONCLUSIONS: In the early stage of the COVID-19 pandemic, a decline in the number of patients initiating first-line treatment was observed as well as a decrease in the proportion of patients receiving CDK4/6i combination treatments and an increase in endocrine monotherapy between March and April 2020. This shift may signal possible diagnosis/treatment initiation delays and prescribing shifts among patients initiating new treatments. Ongoing follow up of these trends through the pandemic is planned to track whether these shifts are sustained and to identify demographic and clinical factors associated with variations in treatment at different stages of COVID-19 epidemic in the US. Citation Format: Samantha Kurosky, Xianchen Liu, Aster Meche, Rebecca Levin, Amy Sullivan, Lynn McRoy. First-line treatment trends in metastatic breast cancer before and at the early stage of the COVID-19 pandemic in the United States [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-21.