BRAF mutational status is associated with survival outcomes in locally advanced resectable and metastatic NSCLC

Background: Immunotherapy-based treatments have demonstrated high efficacy in patients with advanced and locally advanced non-small-cell lung cancer (NSCLC). BRAF mutations affect a small but significant fraction of NSCLC. The efficacy of these therapies in this subgroup of patients is unknown. Mate...

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Detalles Bibliográficos
Autores: Provencio, M, de Lope, LR, Serna-Blasco, R, Nadal, E, Tain, PD, Massuti, B, González-Larriba, JL, Insa, A, Sánchez-Hernández, A, Casal-Rubio, J, Garcia-Campelo, R, López, SS, Rogado, J, Martínez-Martí, A, Bosch-Barrera, J, Bernabé, R, Estévez, SV, Ponce, S, de Castro, J, Sarto, JC, Reguart, N, Dómine, M, Aguilar, A, Majem, M, Estival, A, Cabia, SP, Martín, AL, González, MAS, Cobo, M, Camps, C, Barneto, I, Calvo, V, Collazo-Lorduy, A, Cruz-Bermúdez, A, Romero, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p11181
Acceso en línea:https://isabial.portalinvestigacion.com/publicaciones11181
https://www.lungcancerjournal.info/article/S0169-5002(24)00399-4/fulltext
Access Level:acceso abierto
Palabra clave:BRAF
NSCLC
Immunotherapy
Descripción
Sumario:Background: Immunotherapy-based treatments have demonstrated high efficacy in patients with advanced and locally advanced non-small-cell lung cancer (NSCLC). BRAF mutations affect a small but significant fraction of NSCLC. The efficacy of these therapies in this subgroup of patients is unknown. Materials and methods: Plasma and tissue samples from 116 resectable stage IIIA/B NSCLC patients, included in NADIM and NADIM II clinical trials (NADIM cohort), and from a prospective academic cohort with 84 stage IV NSCLC patients (BLI-O cohort), were analyzed by next-generation sequencing. Results: The p.G464E, p.G466R, p.G466V, p.G469V, p.L597Q, p.T599I, p.V600E (n = 2) BRAF mutations, were identified in four (3.45 %) samples from the NADIM cohort, all of which were cases treated with neoadjuvant chemoimmunotherapy (CH-IO), and four (4.76 %) samples from the BLI-O cohort, corresponding to cases treated with first-line immunotherapy (n = 2) or CH-IO (n = 2). All these patients were alive and had no evidence of disease at data cut-off. Conversely, patients with BRAF wild-type (wt) tumors in the BLI-O cohort had a median progression-free survival (PFS) of 5.49 months and a median overall survival (OS) of 12.00 months (P-LogRank = 0.013 and 0.046, respectively). Likewise, PFS and OS probabilities at 36 months were 60.5 % and 76.1 % for patients with BRAF-wt tumors in the NADIM cohort. The pathological complete response (pCR) rate after neoadjuvant CH-IO in patients with BRAF-positive tumors (n = 4) was 100 %, whereas the pCR rate in the BRAF-wt population was 44.3 % (RR: 2.26; 95 % CI: 1.78-2.85; P < 0.001). Conclusion: BRAF mutations may be a good prognostic factor for advanced and locally advanced NSCLC patients undergoing immunotherapy-based treatments.

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