# EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)

Source: https://onco.cc/terms/egfr-mutation-subtypes/  
OnCo record `egfr-mutation-subtypes` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: EGFR-mutant; EGFR-mutated; EGFR mutation; EGFR mutations; EGFR-positive; exon 19 deletion; exon 19 del; ex19del; L858R; exon 20 insertion; exon 20 ins; ex20ins; T790M; C797S; uncommon EGFR mutations; G719X; S768I; L861Q; EGFR-TKI; EGFR TKI; EGFR inhibitor; EGFR inhibitors

## Notes

- Measured, not asserted. In 2,653 lung adenocarcinoma samples the classes split as exon 19 deletion 382 (14.4%), L858R 289 (10.9%), exon 20 insertion 47 (1.8%), G719X 57, L861Q 30, S768I 30, with T790M in 91 and C797S in 19 of the same treated cohort (cBioPortal luad_mskcc_2023_met_organotropism). The ordering flips by ancestry: in 302 East Asian adenocarcinomas L858R leads exon 19 deletion, 63 against 57, and the overall EGFR rate is 47.4% against 12.4% in the resected TCGA series (Chen 2020). Never-smoker whole genomes read 28.4% EGFR with exon 19 deletion at 38 and L858R at 20 of 232 (Zhang 2021). The classes are not interchangeable for treatment: exon 20 insertions respond to a different set of medicines, and the uncommon alleles do better on a second-generation inhibitor.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Epidermal_growth_factor_receptor
- Wikipedia: https://en.wikipedia.org/wiki/Epidermal_growth_factor_receptor

## Connected records

- terms: [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Driver mutation](https://onco.cc/terms/driver-mutation/), [On-target resistance mutations (gatekeeper, solvent-front, compound)](https://onco.cc/terms/gatekeeper-mutation/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/)
- cancers: [EGFR-mutated non-small-cell lung cancer](https://onco.cc/cancers/egfr-mutant-nsclc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- targets: [EGFR](https://onco.cc/targets/egfr/)
- drugs: [Afatinib](https://onco.cc/drugs/afatinib/), [Aumolertinib](https://onco.cc/drugs/aumolertinib/), [Erlotinib](https://onco.cc/drugs/erlotinib/), [Furmonertinib](https://onco.cc/drugs/furmonertinib/), [Gefitinib](https://onco.cc/drugs/gefitinib/), [Osimertinib](https://onco.cc/drugs/osimertinib/), [Sunvozertinib](https://onco.cc/drugs/sunvozertinib/)
- trials: [ADAURA](https://onco.cc/trials/adaura/), [LUX-Lung 3](https://onco.cc/trials/lux-lung-3/)
- key papers: [Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M](https://onco.cc/key-papers/paper-thress-nat-med/), [Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain](https://onco.cc/key-papers/paper-pao-egfr-t790m-acquired-resistance-plos-med-2005/), [Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib](https://onco.cc/key-papers/paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018/), [EGFR mutation and resistance of non-small-cell lung cancer to gefitinib](https://onco.cc/key-papers/paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005/), [Genomic and evolutionary classification of lung cancer in never smokers](https://onco.cc/key-papers/paper-zhang-lung-cancer-never-smokers-nat-genet-2021/), [Genomic landscape of lung adenocarcinoma in East Asians](https://onco.cc/key-papers/paper-chen-east-asian-lung-adenocarcinoma-nat-genet-2020/), [Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors](https://onco.cc/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/)
- biomarkers: [EGFR C797S (and its phase with T790M)](https://onco.cc/biomarkers/egfr-c797s/), [EGFR exon 19 deletion](https://onco.cc/biomarkers/egfr-exon-19-deletion/), [EGFR exon 20 insertion](https://onco.cc/biomarkers/egfr-exon-20-insertion/), [EGFR L858R](https://onco.cc/biomarkers/egfr-l858r/), [EGFR T790M](https://onco.cc/biomarkers/egfr-t790m/)

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