Treatment Sequences in BRAF-V600–Mutated NSCLC: First-Line Targeted Therapy Versus First-Line (Chemo-) Immunotherapy
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Targeted treatment of patients with metastatic BRAF-V600-mutated NSCLC using BRAF/MEK-inhibitors is effective but limited by acquired resistance. Patients with BRAF-mutant NSCLC may derive long-lasting benefit from immune checkpoint inhibition with programmed death-1/programmed death-ligand 1 (PD-L1) antibodies (immuno-oncology [IO]). Although IO is the preferred first-line therapy in BRAF-mutated melanoma, the optimal treatment sequence in BRAF-mutated NSCLC is not defined. METHODS: This retrospective study investigated the clinical outcome of patients with metastatic BRAF-V600-mutated NSCLC diagnosed in the German national Network Genomic Medicine Lung Cancer. RESULTS: We identified 205 patients with BRAF-V600-mutated NSCLC; 175 patients received first-line therapy with dabrafenib/trametinib (DAB/TRM, 65.1%), IO alone (19.4%), or chemotherapy-IO (15.4%). Overall survival (OS) and time-to-treatment failure of first-line therapy was identical for patients receiving first-line DAB/TRM (median OS 28.0 months) or chemo/IO (27.8 months, hazard ratio [HR] 1.1, p = 0.68). Female patients had superior OS (HR 0.65, p = 0.049, confirmed in multivariate model), which was mainly driven by superior OS of female to that of male patients receiving first-line DAB/TRM (OS HR 0.53, p = 0.015). There was no sex difference in survival of patients receiving IO-based first-line treatment (OS HR 1.02). Surprisingly, high PD-L1 status (tumor proportion score ≥50%) was associated with shortened time-to-treatment failure in first-line treatment (HR 1.83, p = 0.002, confirmed in multivariate models adjusting for sex; OS with nonsignificant trend, HR 1.4), regardless of whether the first-line regimen was IO-based or targeted therapy. CONCLUSIONS: Targeted or IO-based first-line treatment of BRAF-V600-mutated NSCLC has similar survival outcomes. Sex and PD-L1 status may support decision-making at the individual patient level.
Source: Journal of Thoracic Oncology
Authors: Marcel Wiesweg, Ali Alaffas, Anna Rasokat, Felix Carl Saalfeld, Maximilian Rost, Christin Assmann, Franziska Herster, Moritz Hilbrandt, Frank Griesinger, Anna Kron, Julia Roeper, Franziska Glanemann, Cornelia Kropf-Sanchen, Martin Reck, Jonas Kulhavy, Albrecht Stenzinger, Jürgen Wolf, Martin Sebastian, Martin Schuler, Martin Wermke, Nikolaj Frost, Hans-Georg Kopp, Petros Christopoulos, Matthias Scheffler
Institutions: Essen University Hospital, University of Cologne, University Hospital Cologne, National Center for Tumor Diseases, Nationales Centrum für Tumorerkrankungen Dresden, Technische Universität Dresden, University Hospital Frankfurt, Heidelberg University, University Hospital Heidelberg, Humboldt-Universität zu Berlin, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Charité - Universitätsmedizin Berlin, Carl von Ossietzky Universität Oldenburg, Pius Hospital Oldenburg, Universität Ulm, University Hospital Ulm, German Center for Lung Research, LungenClinic Grosshansdorf, Comprehensive Cancer Center Mainfranken, Universitätsklinikum Würzburg, German Cancer Research Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,100
Funder: Deutsche Krebshilfe
OpenAlex ID: W4410199457