ORIGINAL RESEARCH article
Front. Oncol.
Sec. Thoracic Oncology
This article is part of the Research TopicReal-World Data and Real-World Evidence in Lung Cancer Volume IIView all 18 articles
Outcomes with Frontline Immune Checkpoint Inhibitors Among Individuals with BRAF-Mutant Non-Small Cell Lung Cancer
Provisionally accepted
Julian A. Marin-Acevedo1
Ram Thapa2Sudeepthi V. Bandikatla3,4
Dung-Tsa Chen2
J. Kevin Hicks3
Jhanelle Elaine Gray5
Sonam Puri5*- 1Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, United States
- 2Moffitt Cancer Center Department of Biostatistics and Bioinformatics, Tampa, United States
- 3Moffitt Cancer Center, Tampa, United States
- 4University of South Florida, Tampa, United States
- 5Moffitt Cancer Center Thoracic Oncology Program, Tampa, United States
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Background Oncogenic BRAF mutations affect ~4% of non-small cell lung cancer (NSCLC). Class I mutations (i.e., V600) are typically responsive to BRAF/MEK inhibitors, while non-Class I are often resistant. The role of immune checkpoint inhibitors (ICIs) as first-line therapy in BRAF-mutant NSCLC remains unclear. Methods We retrospectively analyzed patients with BRAF-mutant NSCLC treated at Moffitt Cancer Center from January 1, 2012, to August 9, 2023. Demographics, biomarker (e.g., PD-L1, molecular profile), and treatment data were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using standardized real-world endpoints. Results Among 122 individuals, 54 had Class I and 68 had non-Class I mutations. For Class I mutations, ICIs yielded a PFS of 9.2 months and OS of 42.2 months, representing a significant OS advantage over chemotherapy-alone (22.2 months; p=0.03). Outcomes were comparable to those seen with anti-BRAF/MEK therapy (PFS 14.7 months; p=0.49, OS NE; p=0.99), while ICIs trended towards improved OS in those with PD-L1 ≥50% (53.1 vs. 24.8 months; p=0.61). For non-Class I mutations, ICI benefit was more limited (PFS 11.7 months, OS 18.5 months) yet compared favorably to chemotherapy-alone (PFS 4.7 months; p=0.01; OS 9.9 months; p=0.22). No patients with non-Class I mutations received anti-BRAF/MEK therapy. Conclusion ICIs appear effective in BRAF mutant-NSCLC. For Class I mutations, ICIs yielded significant survival benefit over chemotherapy-alone. Outcomes were comparable to anti-BRAF/MEK therapy, with a potential survival advantage favoring ICIs in those with PD-L1 ≥50%. For non-Class I mutations, ICIs benefit was more modest but compared favorably to chemotherapy-alone.
Keywords: BRAF mutations, NSCLC, Adenocarcinoma, Smoking, driver mutations, PD-L1, Immunotherapy, targeted therapy
Received: 06 Aug 2025; Accepted: 21 Nov 2025.
Copyright: © 2025 Marin-Acevedo, Thapa, Bandikatla, Chen, Hicks, Gray and Puri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sonam Puri, sonam.puri@moffitt.org
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