Unveiling the Landscape of Uncommon EGFR Mutations in NSCLC-A Systematic Review.
J Thorac Oncol
; 19(7): 973-983, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38499147
ABSTRACT
Uncommon EGFR mutations represent a rare subgroup of NSCLC. Data on the efficacy of different generations of tyrosine kinase inhibitors (TKIs) in these rare mutations are scattered and limited to mostly retrospective small cohorts because these patients were usually excluded from clinical trials. This was a systematic review on the efficacy of TKIs in patients harboring uncommon EGFR mutations, defined as mutations other than exon 20 insertions mutations or T790M. Response rates (RRs) for different generations of TKIs were determined for individual uncommon mutations, compound mutations, and according to classical-like and P-loop alpha helix compressing mutations classes. This study was conducted in accordance with the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 1836 patients from 38 studies were included in the final analysis. Most available data (92.6%) were from patients treated with first- or second-generation TKIs. G719X, S768I, E709X, L747X, and E709-T710delinsD showed RRs ranging from 47.8% to 72.3% to second-generation TKIs, generally higher than for first- or third-generation TKIs. L861Q mutation exhibited 75% (95% confidence interval [CI] 56.6%-88.5%) RRs to third-generation TKIs. Compound mutations with G719X, E709X, or S768I consistently showed RRs above 50% to second- and third-generation TKIs, although fewer data were available for third generations. For classical-like mutations, RRs were 35.4% (95% CI 27.2%-44.2%), 51.9% (95% CI 44.4%-59.3%), and 67.9% (95% CI 47.6%-84.1%) to first-, second-, and third-generation TKIs, whereas for P-loop alpha helix compressing mutations classes mutations, RRs were 37.2% (95% CI 32.4%-42.1%), 59.6% (95% CI 54.8%-64.3%), and 46.3% (95% CI 32.6%-60.4%), respectively. This systematic review supports the use of second-generation TKI afatinib for G719X, S768I, E709X, and L747X mutations and for compound uncommon mutations. For other uncommon mutations such as L861Q, third-generation TKI, such as osimertinib, could also be considered, given its activity and toxicity profile.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
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Inibidores de Proteínas Quinases
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Receptores ErbB
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Neoplasias Pulmonares
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Mutação
Limite:
Humans
Idioma:
En
Revista:
J Thorac Oncol
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J. thorac. oncol
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Journal of thoracic oncology
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suíça