O câncer de pulmão de células não pequenas (CPCNP) avançado ou metastático com deleção confirmada do éxon 19 do EGFR ou mutação pontual EGFR L858R constitui um subgrupo molecularmente definido com sua própria via de tratamento de primeira linha dedicada.
A deleção do éxon 19 e a substituição L858R respondem juntas por aproximadamente 85% a 90% de todas as mutações EGFR no CPCNP. Ambas as alterações ativam o domínio da tirosina quinase e estão associadas à sensibilidade a inibidores de tirosina quinase (TKIs) do EGFR de pequenas moléculas, tornando os testes moleculares essenciais antes de iniciar o tratamento.
The two most common EGFR mutations in NSCLC are exon 19 deletions and L858R; these represent approximately 85% to 90% of all EGFR mutations in NSCLC.
Both result in activation of the tyrosine kinase domain and are associated with sensitivity to small-molecule EGFR tyrosine kinase inhibitors (TKIs).
In the first-line setting, the NCCN NSCLC Panel recommends the following as preferred and category 1 options for patients with advanced or metastatic NSCLC with EGFR exon 19 deletion or L858R mutation: single-agent osimertinib, osimertinib in combination with (carboplatin or cisplatin)/pemetrexed (for nonsquamous histology), or lazertinib + amivantamab-vmjw.
Single-agent afatinib, dacomitinib, erlotinib, gefitinib, or lazertinib are first-line treatment options that may be useful in certain circumstances.
Erlotinib in combination with bevacizumab (if nonsquamous and no recent history of hemoptysis) or erlotinib in combination with ramucirumab are also first-line treatment options that may be useful in certain circumstances.
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