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.

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.

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. Provencio declares consulting fees, payment for lectures, presentations or speakers bureaus and support for attending meetings and/or travel from BRISTOL-MYERS SQUIBB, Astra Zeneca, MSD, Roche, Takeda. This author has also declared that he have a pending patent (n° EP 22 382 701.5). R. Serna-Blasco declares to be in possession of a pending patent (n° EP 22 382 701.5). E. Nadal declares Grants or contracts from Roche, Pfizer, Bristol-Myers Squibb and Merck Serono; consulting fees from Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Sanofi, Pfizer, Lilly, Janssen, AMGEN, Daiichi-Sankyo, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, Qiagen, and Bayer; payment for lectures, presentations or speakers bureaus from Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Sanofi, Pfizer, Lilly, Janssen, Amgen, Boehringer-Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre and Qiagen; support for attending meetings and/or travel from Roche, Takeda and Pfizer; and Participation on data safety Monitoring board or advisory board from Roche, Apollomics and MSD. M.P. Diz Taín declares Payment or honoraria for lectures, presentations or speakers bureaus from BRISTOL-MYERS SQUIBB, Astra-Zeneca, Roche, MSD, Takeda, Pfizer and Amgen; support for attending meetings and/or travel from BRISTOL-MYERS SQUIBB, Roche, MSD and Takeda; Participation on a Data Safety Monitoring Board or Advisory Board from BRISTOL-MYERS SQUIBB, Astra-Zeneca, and Boehringer Ingelheim; and other financial or non-financial interests from Astra-Zeneca, Roche, Mirati, and Pfizer. B. Massuti declares consulting fees and support for attending meetings and/or travel from Bristol-Myers Squibb, Takeda, Merck Sharpe and Dohme. J.L. González Larriba declares consulting fees from MSD, Janssen Cilag, Bristol Myers Squibb, Boehringer Ingelheim, and AMGEN; Payment or honoraria for lectures, presentations or speakers bureaus from MSD, Astra Zeneca, Roche, Pfizer, Janssen-Cilag, Novartis, Astella Pharma, and Bristol-Myers Squibb; Support for attending meetings and/or travel from MSD, Takeda, Bristol-Myers Squibb, Roche, Pfizer, and Janssen-Cilag. A. Insa declares Payment or honoraria for lectures, presentations or speakers bureaus from AMGEN, Bristol-Myers Squibb, Roche, and Takeda; Support for attending meetings and/or travel from Roche, Pfizer, and MSD; Participation on a Data Safety Monitoring Board or Advisory Board from Astra Zeneca, Sanofi, and Pfizer. A. Sánchez-Hernández declares Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Lilly, MSD, Sanofi, Astra Zeneca, Janssen, Takeda, Merck, Novartis, Pfizer, and Bristol-Myers Squibb; Support for attending meetings and/or travel from Roche, Sanofi, MSD Takeda, Janssen, Pfizer, and Bristol-Myers Squibb. R. García-Campelo declares Grants or contracts from Bristol-Myers Squibb, Astra Zeneca, and MSC; consulting fees from Roche, Bristol-Myers Squibb, MSD, Sanofi, Takeda, Pfizer, Regeneron, AMGEN, and Astra Zeneca. J. Rogado declares Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Astra Zeneca, MSD, MERCK, Ferrer, Persan Farma, Fresenius Kabi, and Sanofi; Support for attending meetings and/or travel from Roche, MSD, Bristol-Myers Squibb, Astra Zeneca, and Lilly; Participation on a Data Safety Monitoring Board or Advisory Board from Fresenius Kabi, MSD, Sanofi. A. Martínez-Martí declares consulting fees from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche AG, MSD, and Pfizer; Payment or honoraria for lectures, presentations, speakers bureaus from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche AG, MSD, MSD, and Pfizer; Payment for expert testimony from AstraZeneca/MedImmune; Support for attending meetings and/or travel from AstraZeneca/MedImmune, Bristol-Myers Squibb, F. Hoffmann La Roche AG, MSD, Pfizer, and Lilly; Participation on a Data Safety Monitoring Board or Advisory Board from AstraZeneca/MedImmune, MSD, F. Hoffmann La Roche, Bristol-Myers Squibb. J. Bosch-Barrera declares consulting fees from Sanofi and Roche; Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Bristol-Myers Squibb, Astra Zeneca, and Pfizer; Support for attending meetings and/or travel from Takeda and MSD. R. Bernabé-Caro declares an investigational grant Roche; Payment or honoraria for lectures, presentations, speakers bureaus from Roche, Bristol-Myers Squibb, Pfizer, MSD, Amgen, Takeda, and Astra Zeneca; Participation on a Data Safety Monitoring Board or Advisory Board from Takeda, Roche, Bristol-Myers Squibb, and Astra Zeneca. J. de Castro Carpeño declares consulting from fees Astra Zeneca, Bristol Myers Squibb, Hoffmann- La Roche, MSD, Boehringer Ingelheim, Janssen, Lilly, Sanofi, Takeda, Pfizer, and Glaxo; Payment or honoraria for lectures, presentations, speakers bureaus from Astra Zeneca, Bristol Myers Squibb, Hoffmann- La Roche, MSD, Pfizer, Janssen, Takeda, and Sanofi; Support for attending meetings and/or travel from Astra Zaneca, MSD, and Hoffmann- La Roche; Participation on a Data Safety Monitoring Board or Advisory Board from Astra Zeneca, Bristol Myers Squibb, Hoffmann- La Roche, MSD, Glaxo, Janssen, Gilead, and Sanofi. N. Reguart declares Payment or honoraria for lectures, presentations or speakers bureaus from MSD, Bristol Myers Squibb, Roche, Boehringer Ingelheim, Guardant Health, Bayer, Merck, Pfizer, Takeda, Novartis, Astra-Zeneca, Janssen Oncology, Sanofi, Eli Lilly, and Amgen; Support for attending meetings and/or travel from Roche, Takeda, and MSD. M. Dómine declares consulting fees and Payment or honoraria for lectures, presentations or speakers bureaus from Astra Zeneca, Bristol-Myers Squibb, MSD, Pfizer, Roche, and Takeda; Support for attending meetings and/or travel from Astra Zeneca, MSD, Pfizer, and Takeda. M. Majem declares Grants or contracts from Roche and Astra Zeneca; Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Astra Zeneca, MSD, Pfizer, Helsinn, Cassen, AMGEN, Janssen, Sanofi, Pierre Fabre, Bristol-Myers Squibb, and Takeda; Support for attending meetings and/or travel from Astra Zeneca, MSD, and Roche. A. Estival declares Payment or honoraria for lectures, presentations or speakers bureaus from MSD, Pharmamar, Astra Zeneca, Takeda, Roche, and GSK; Support for attending meetings and/or travel from MSD, Boehringer Ingelheim, and Pharmamar; Participation on a Data Safety Monitoring Board or Advisory Board from Roche and MSD. A. López Martín declares Payment or honoraria for lectures, presentations, speakers bureaus from GSK, Bristol-Myers Squibb, and Astra Zeneca; Support for attending meetings and/or travel from Pfizer and Takeda. M. A. Sala González declares Payment or honoraria for lectures, presentations or speakers bureaus from Takeda and Roche; Support for attending meetings and/or travel from Roche and PharmaMar. M. Cobo declares consulting fees from Novartis, Roche, Astra Zeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, MSD, Lilly, Takeda, Pfizer, Kyowa, Sanofi, and Jansen. Payment or honoraria for lectures, presentations or speakers bureaus from Novartis, Astra Zeneca Boehringer-Ingelheim, Bristol-Myers Squibb, Roche, Lilly, MSD, Takeda, Kyowa, Pierre-Fabre, Novocure, Sanofi, and Jansen. I. Barneto declares Payment or honoraria for lectures, presentations or speakers bureaus from Bristol-Myers Squibb, Astra Zeneca, MSD, Takeda, AMGEN, and Novartis; Support for attending meetings and/or travel from MSD and Astra Zeneca; Participation on a Data Safety Monitoring Board or Advisory Board from Sanofi. V. Calvo declares consulting fees from Roche, Astra Zeneca, MSD, Bristol-Myers Squibb, Takeda, Sanofi, and AMGEN; Payment or honoraria for lectures, presentations or speakers bureaus from Roche, Astra Zeneca, MSD, Bristol-Myers Squibb, Takeda, Pfizer, and Janssen; Support for attending meetings and/or travel from Astra Zeneca, Roche, and Takeda. A. Collazo declares Payment or honoraria for lectures, presentations or speakers bureaus from Astra Zeneca and Janssen; Support for attending meetings and/or travel from MSD and Takeda. A. Romero declares consulting fees from Takeda; Payment or honoraria for lectures, presentations or speakers bureaus from Illumina, Health in code, and Thermofisher. Support for attending meetings and/or travel from Thermofisher Scientific. Bristol Myers Squibb Foundation, and Takeda; the author also declares a pending patent (n° EP 22 382 701.5). The rest of the authors declare no potential conflicts of interest.