EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)
Lung cancers with a mutated EGFR gene are treated with EGFR pills, but which pill and how well it works depends on exactly where the mutation is. Exon 19 deletions and L858R are the 'classic' sensitive ones; exon 20 insertions resist most pills; T790M and C797S appear when resistance develops.
EGFR mutations occur in about 15% of Western and 40-50% of East Asian lung adenocarcinomas, mostly in never-smokers. Exon 19 deletions (best outcomes) and L858R respond to osimertinib, now standard first line (FLAURA) and adjuvant (ADAURA), with amivantamab-lazertinib (MARIPOSA) or osimertinib plus chemotherapy (FLAURA2) as intensified options. Exon 20 insertions need amivantamab or sunvozertinib. T790M was the resistance mutation to first-generation TKIs that osimertinib overcame; C797S and MET amplification are the main escape routes from osimertinib. Testing is by tissue NGS or plasma ctDNA at diagnosis and at progression.
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