9521 Background: Whether disease attributes such as tumor burden or central nervous system (CNS) metastases can affect outcomes for patients with BRAF+ metastatic melanoma (MM) is currently unclear. This study examined real-world patient characteristics, treatment patterns, and clinical outcomes among subgroups of patients with BRAF+ MM treated with dabrafenib + trametinib (dab/tram) in the United States. Methods: This retrospective cohort study used the nationwide Flatiron Health electronic health record-derived de-identified database from 1/1/2014 to 9/30/2021. Included patients were aged ≥18 years with a diagnosis of BRAF+ MM and received first-line (1L) dab/tram. Patients were stratified into 4 subgroups: high tumor burden (HTB; ≥3 sites of metastasis and lactate dehydrogenase [LDH] ≥333 IU/L), low tumor burden (LTB; <3 sites of metastasis and LDH <333 IU/L), with CNS metastases (prior to 1L dab/tram), and without CNS metastases (prior to 1L dab/tram). Patient characteristics and treatment patterns were evaluated descriptively. Given the potential patient overlap between subgroups, no comparative statistics were conducted. Real-world progression-free (rwPFS) and overall survival (OS) were explored from dab/tram initiation. Results: Among 460 included patients (mean age 60 years, 64% male), 66 (14%) had a HTB, 69 (15%) had a LTB, 164 (36%) had CNS metastases, and 296 (64%) did not. Patient characteristics were comparable across the subgroups. Over 60% of HTB patients had documented metastases in each of the liver, lung, bone, lymph nodes, and other sites. Only lung metastases had >60% prevalence among patients with a LTB. Overall, 51% of the included patients went on to receive a second-line therapy; LTB patients and those without CNS metastases had a longer time to next therapy. The median rwPFS and OS were significantly shorter among patients with a HTB vs LTB, and among patients with vs without CNS metastases (Table). Conclusions: Both tumor burden and presence of CNS metastases appear to have a significant impact on survival among BRAF+ MM patients treated with 1L dab/tram. With growing use of 1L immunotherapy in MM, 1L BRAF/MEK inhibitors are increasingly being used in patients with a worse prognosis, which may explain the lower rwPFS and OS with dab/tram when compared with clinical trials. [Table: see text]
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