A real world analysis of secondary BRAF variations after targeted therapy resistance in driver gene positive NSCLC

Secondary BRAF variations have been identified as a mechanism of resistance to tyrosine kinase inhibitors (TKIs) in patients with driver gene-positive NSCLC. Nevertheless, there is still a lack of consensus regarding the characteristics and subsequent treatment strategies for these patients. We retr...

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Bibliographic Details
Published in:Scientific reports 2024-09, Vol.14 (1), p.20302-12, Article 20302
Main Authors: Liu, DuJiang, Ding, KaiBo, Yin, KaiLai, Peng, ZhongSheng, Li, Xinyue, Pan, Yang, Jin, XuanHong, Xu, YanJun
Format: Article
Language:English
Subjects:
631/67/1059/602
631/67/1612
631/67/1857
Adult
Aged
BRAF
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - mortality
Carcinoma, Non-Small-Cell Lung - pathology
Characteristics
Chemotherapy
Drug Resistance, Neoplasm - genetics
Female
Humanities and Social Sciences
Humans
Inhibitors
Kinases
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Male
Medical records
MEK inhibitors
Middle Aged
Molecular Targeted Therapy - methods
multidisciplinary
Mutation
NSCLC
Patients
Protein Kinase Inhibitors - therapeutic use
Proto-Oncogene Proteins B-raf - antagonists & inhibitors
Proto-Oncogene Proteins B-raf - genetics
Retrospective Studies
Science
Science (multidisciplinary)
Secondary variations
Signal transduction
Survival
Treatment strategies
Tyrosine kinase inhibitors
Variation
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Description
Summary:Secondary BRAF variations have been identified as a mechanism of resistance to tyrosine kinase inhibitors (TKIs) in patients with driver gene-positive NSCLC. Nevertheless, there is still a lack of consensus regarding the characteristics and subsequent treatment strategies for these patients. We retrospectively reviewed the medical records of patients with driver gene-positive NSCLC who received TKIs therapy at Zhejiang Cancer Hospital between May 2016 and December 2023. The clinical and genetic characteristics of these patients were assessed, along with the impact of various treatment strategies on survival. This study enrolled 27 patients with advanced NSCLC, in whom BRAF variations occurred at a median time of 28 months after the initiation of targeted therapy. The multivariate accelerated failure time (AFT) model revealed that, compared to chemotherapy-based regimens group, the combined targeted therapy group (p 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-71143-6