Abstract Background: CDK4/6 inhibitor in combination with an aromatase inhibitor (AI) or fulvestrant as initial endocrine therapy are standard of care for patients with HR+/HER2– advanced/metastatic breast cancer (mBC). This analysis describes treatment patterns including dosing patterns and time to subsequent treatment in patients receiving first line Palbociclib (PB)+AI therapy compared to AI alone, for HR+/HER2– mBC in the US routine clinical setting. Methods: This was a retrospective analysis of Flatiron Health’s nationwide longitudinal electronic health records from over 280 cancer clinics representing more than 3 million actively treated cancer patients in the US. Between February 2015 and March 2020, 2888 postmenopausal mBC women and men aged ≥18 years started first-line PB+AI or AI therapy. Patients were followed from start of therapy to September 2020, death, or last visit, whichever came first. PB treatment patterns were captured as starting dose and dose adjustments from medical records during the observation period. Comparative time to subsequent therapy (TTNT) or chemotherapy (TTC) was defined as length of time from the start of treatment to next line of anticancer therapy/chemotherapy, death from any cause, last visit, or end of study, whichever came first. Cox proportional-hazards models were used to estimate the relative effectiveness of PB+AI vs AI. Stabilized inverse probability treatment weighting (sIPTW) and propensity score matching (PSM) statistical methods were used to balance of baseline demographics and clinical characteristics. Results: Of the 2888 eligible pts (1324 with PB+AI and 1564 with AI), median age was 70.0 years, 67.8% were white, 34.8% had de novo mBC, 29.4% had lung or liver involvement, 38.7% had bone-only disease. Median follow-up was 25.0 months in the PB+AI arm and 23.3 months in the AI alone arm. Of the 1342 patients receiving PB, therapy was started at 125 mg, 100 mg, and 75 mg/day in 83.8%, 10.9%, 3.6%, respectively (1.7% undocumented PB dose) with dose changes in 41.1%, 36.8%, 31.3% of patients in each starting dose category with dosing information. After sIPTW median TTNT was 18.4 months (95%CI: 16.3-20.3) in the PB +AI group and 8.3 months (95%CI: 7.2-10.0) in the AI group; HR=0.56 (95%CI: 0.51-0.62), p< 0.0001. After sIPTW median TTC was 37.4 months (95%CI: 33.7-40.7) PB+AI group and 29.2 months (95%CI: 26.8-33.5) in the AI group; HR=0.77 (95%CI: 0.69-0.86), p< 0.0001. Results for the PSM analyses were similar. The table presents full results in detail. Conclusions: These treatment patterns analyses in a heterogeneous mBC patients from real world US clinical practice, provide support for first line PB+AI treatment for HR+/HER2– mBC. The majority of patients initiated therapy at the 125 mg/daily dose (84%). Importantly, these analyses also report meaningful differences in the delay to next line of therapy and chemotherapy in the PB+AI compared to AI therapy arm. Table. Median time to next line of therapy or chemotherapy Citation Format: Hope Rugo, Xianchen Liu, Benjamin Li, Lynn McRoy, Connie Chen, Rachel M. Layman, Adam M. Brufsky. Real-world treatment patterns of Palbociclib plus an aromatase inhibitor or aromatase inhibitor alone for metastatic breast cancer in the Flatiron database [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-14.