Abstract Background:There is limited real-world (RW) evidence describing treatment patterns among oncologists since clinical guidelines have established a preference for CDK4/6 inhibitors (CDK4/6i) plus an aromatase inhibitor (AI) or fulvestrant for first-line (1L) HR+/HER2- mBC. The objective of this RW study was to assess the influence of common clinical attributes on prescriber trends in 1L HR+/HER2- mBC by conducting a Discrete Choice Experiment (DCE) and evaluating the clinical decision-making via retrospective medical chart review. Methods:Via a web-based instrument, medical oncologists were presented four hypothetical clinical scenarios (CS) to assess the influence of three clinical attributes on CDK4/6i prescribing preference via DCE: pre-menopausal (pre-M) vs post-M, prior adjuvant (PA) vs no PA, and bulky liver metastases (BuLM) vs no or unknown BuLM. Respondents selected their preferred 1L treatment for each CS: single-agent chemotherapy, combination chemotherapy, hormonal therapy, or CDK4/6i. Proportion of providers selecting CDK4/6i were reported in each scenario (e.g., pre-M vs post-M). Next, a planned subset of providers completed a physician chart abstraction (PCA) summarizing demographics, clinical characteristics, 1L and subsequent regimens for HR+/HER2- mBC patients 18 years or older at diagnosis, and who initiated ≥1 line of mBC therapy. Descriptive statistics were used to examine differences between preferred (via DCE) 1L regimens (hormonal therapy, CDK4/6i, chemotherapy) and PCA 1L regimens (chart review). Results:47 medical oncologists from all U.S. census regions participated in the DCE, of which 17 completed 52 unique PCAs. Provider characteristics: mean 22.7 (5, 50) years in practice; mean 23.3 (3, 80) unique HR+/HER2- mBC patients treated monthly. PCA patient characteristics: median age 61 (38, 87) years; post-M = 88.5% and PA = 40.4% (Table 1). Across DCE and PCA patients, overall 1L CDK4/6i preference was 67.6% (DCE) and 84.6% (PCA) (Table 1). By patient attribute, CDK4/6i DCE preference and PCA use were, respectively: pre-M= 55% vs 67%; post-M = 80% vs 87%; PA= 66% vs 87%, no PA = 70% vs 83%. CDK4/6i preference for patients with BuLM was 55% but could only be assessed in DCE (Table 2). Chemotherapy as an alternative to, or prior to, CDK4/6i was 23.3% in DCE (19.1% vs 4.2%) and 5.8% in PCA (5.8% vs 0%). Conclusion:Our research demonstrates that RW use of a CDK4/6i regimen in 1L HR+/HER2- mBC is higher than reported preference for CDK4/6i as assessed through DCE overall and in all CS. CDK4/6i preference in DCE was lowest for pre-M (55%) and PA (66%), while RW use was above 80% in all cases except for pre-M (67%). The use of chemotherapy prior to, or as an alternative to, CDK4/6i was both a preference in DCE and an observation in RW patients, which may relate to continued guideline inclusion of 1L chemotherapy which may warrant additional research to address continued relevance in the CDK4/6i era. Table 1: Patient characteristics, HR+/HER2-DCE(N=188)PCA(N=52)Age, mean (median, range)54 (54; 38-71)61 (63; 38-87)Menopausal status, n (%)Pre-menopause94 (50)6 (11.6)Post-menopause94 (50)46 (88.5)Prior adjuvant therapy, n (%)94 (50)21 (40.4)CDK4/6i0 (0)3 (5.8)Site of Metastases, n (%)Liver94 (50)0 (0)Other/Unknown94 (50)52 (100)1L Therapy, n (%)Hormone-based therapy14 (7.4)5 (9.6)Chemotherapy27 (19.1)3 (5.8)CDK4/6i-based therapy127 (67.6)44 (84.6)Immediately following chemotherapy8 (4.2) Table 2: CDK4/6i use as a function of clinical characteristicsCDK4/6i Usen (%)Pre-M(N=94)Post-M(N=94)PA(N=94)No PA(N=94)BuLM(N=94)No/Unk BuLM(N=94)DCE52 (55)75 (80)62 (66)65 (70)52 (55)75 (80)CDK4/6i Usen (%)Pre-M(N=6)Post-M(N=46)PA(N=23)No PA(N=29)BuLM(N=0)No/Unk BuLM (N=52)PCA4 (67)40 (87)20 (87)24 (83)0 (0)44 (85)p-value.59.30.05.15NA.47 Citation Format: Bruce Feinberg, Igoni Dokubo, Jeff Wojtynek, Jonathan Kish. Evolution of prescribing trends for HR+/HER2- metastatic breast cancer (mBC) in a post-CDK4/6i world [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 PS7-55.