e13021 Background: Palbociclib (PA) has been approved for HR+/HER2–advanced/metastatic breast cancer (mBC) in combination with an aromatase inhibitor (AI) or fulvestrant for more than 6 years. Regardless of the labeled recommended starting dose of 125mg/day, some patients initiate palbociclib at lower doses in routine practice. This study described real-world starting dose, patient characteristics, and effectiveness outcomes of first line PA+ AI for mBC in the US clinical setting. Methods: We conducted a retrospective analysis of Flatiron Health’s nationwide longitudinal electronic health records, which came from over 280 cancer clinics representing more than 2.2 million actively treated cancer patients in the US. Between February 2015 and September 2018, 813 HR+/HER2– mBC women initiated PA+AI as first-line therapy and had ≥ 3 months of potential follow-up. Patients were followed from start of PA+AI to December 2018, death, or last visit, whichever came first. Real-world progression-free survival (rwPFS) was defined as the time from the start of PA+AI to death or disease progression. Real-world tumor response (rwTR) was assessed based on the treating clinician’s assessment of radiologic evidence for change in burden of disease over the course of treatment. Multivariate analyses were performed to adjust for demographic and clinical characteristics. Results: Of 813 eligible patients, 68.3% were white, median age was 65.0 years, and 42.9% had visceral disease (lung and/or liver). Median duration of follow-up was 21.0 months. 805 patients had records of PA starting dose, with 125mg and 75/100mg/day being 86.5% and 13.5%, respectively. Patients who started at 75/100mg/day were more likely to be ≥75 years than those who started at 125mg/day (38.5% vs 17.1%). Other baseline and disease characteristics were generally evenly distributed. Patients who started at 125mg/day had longer median rwPFS (27.8 vs 18.6 months, adjusted HR=0.74, 95%CI=0.52-1.05) and higher rwTR (54.0% vs. 40.4%) than those patients who started 100/75mg/day (adjusted OR=1.76, 95%CI=1.13-2.74). Table presents results in detail. Conclusions: Most patients in this study initiated palbociclib at 125mg/day and dose adjustment was similar regardless of starting dose. These real-world findings may support initiation of palbociclib at a dose of 125mg/day in combination with AI for the first-line treatment of HR+/HER2- mBC. [Table: see text]