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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Detalhes bibliográficos
Autores: Provencio, Mariano, Robado De Lope, Lucía, Serna-Blasco, Roberto, Nadal, Ernest, Diz Tain, Pilar, Massuti, Bartomeu, González-Larriba, José Luis, Insa, Amelia, Sánchez-Hernández, Alfredo, Casal-Rubio, Joaquín, García-Campelo, Rosario, Sequero López, Silvia, Rogado Revuelta, Jacobo, Martínez-Martí, Alex, Bosch-Barrera, Joaquim, Bernabé, Reyes, Vázquez Estévez, Sergio, Ponce, Santiago, De Castro, Javier, Coves Sarto, Juan, Reguart, Noemí, Dómine, Manuel, Aguilar, Andrés, Majem, Margarita, Estival, Anna, Peña Cabia, Silvia, López Martín, Ana, Sala González, María Ángeles, Cobo, Manuel, Camps, Carlos, Barneto, Isidoro, Calvo, Virginia, Collazo-Lorduy, Ana, Cruz-Bermúdez, Alberto, Romero, Atocha
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/215719
Acesso em linha:https://hdl.handle.net/2445/215719
Access Level:acceso abierto
Palavra-chave:Càncer de pulmó
Mutació (Biologia)
Lung cancer
Mutation (Biology)
Descrição
Resumo: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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