Original articleReal-world outcomes of different lines and sequences of treatment in BRAF-positive advanced melanoma patientsBetof Warner, Allisona; Tarhini, Ahmadb; Kang, Barinderc; Nakasato, Antonioc; Ling, You-Lic; Shah, Rohanc; Tang, Jacksond; Patel, Jeetvanc Author Information aDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York bCutaneous Oncology and Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida cNovartis Pharmaceuticals Corporation, East Hanover, New Jersey dAsclepius Analytics Ltd., New York, New York, USA Received 26 April 2022 Accepted 4 August 2022 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to You-Li Ling, PhD, Novartis Pharmaceuticals Corporation, 1 Health Plaza, East Hanover, NJ 07936, USA, E-mail: [email protected] Melanoma Research: November 16, 2022 - Volume - Issue - 10.1097/CMR.0000000000000856 doi: 10.1097/CMR.0000000000000856 Buy SDC PAP Metrics Abstract The objective of this study is to compare efficacy with different treatment sequences and lines of treatment among BRAF V600 mutated (BRAF+) advanced melanoma patients with immunotherapies (IO) and targeted therapies (TT) using real-world data. This was a retrospective cohort study using the Novartis BRAF+ meLanoma patients ObsErvational database, the harmonized customized data from Flatiron and ConcertAI. The study included BRAF+ advanced unresectable melanoma patients treated with first-line (1L) IO or TT between 1 January 2014 and 31 May 2020. Patient characteristics and treatment patterns were described. Kaplan–Meier curves and propensity score-adjusted Cox models were used for analyzing progression-free survival (PFS) and overall survival (OS). A total of 1961 patients were included, of which, 57.2% received IO and 42.8% received TT on 1L therapy. Overall, 603 patients initiated a 2L therapy: 56.2% IO and 43.8% TT. Regardless of treatment sequence, patients progressed at a relatively similar rate with no significant difference between groups (median PFS: 12.9 months for 1L TT/2L IO and 13.1 months for 1L IO/2L TT; HR, 0.84; P = 0.137). The 2-year OS rate was also similar with 1L TT/2L IO and 1L IO/2L TT (78% vs. 80%; HR, 1.09; P = 0.730). PFS was worse on 2L therapy compared with 1L (median 4.7 vs. 6.5 months). Efficacy on 2L therapy was poor compared with 1L. Among patients who received 2L therapy, regardless of treatment sequences, outcomes were comparable between 1L TT/2L IO and 1L IO/2L TT in this study that reflects real-world experiences beyond clinical trial selective eligibility criteria. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.