# EGFR L858R

Source: https://onco.cc/biomarkers/egfr-l858r/  
OnCo record `egfr-l858r` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

L858R is a single letter change in exon 21 of EGFR that keeps the kinase active. It is the second commonest sensitising mutation and shares every EGFR inhibitor label with the exon 19 deletion.

## Summary

The c.2573T>G substitution in exon 21 replaces leucine 858 with arginine in the activation loop. Labels for osimertinib, erlotinib, gefitinib, afatinib, dacomitinib and amivantamab plus lazertinib name 'exon 21 L858R substitution mutations' alongside exon 19 deletions, and the same companion diagnostics detect both. Trial subgroup analyses (FLAURA, MARIPOSA) show shorter progression-free survival for L858R than for exon 19 deletions on the same drugs, and L858R more often co-occurs with other EGFR variants, which is why some guidelines discuss combination therapy for it.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: L858R; EGFR exon 21 L858R; exon 21 substitution; EGFR L858R mutation; p.L858R
- Tags: biomarker; egfr

## Notes

- Lung cancer: present in 9 to 21% of adenocarcinomas, 20.9% in the East Asian cohort against 10.9% in the largest Western panel series (cBioPortal). It is the commoner classical allele in East Asian disease and the less responsive one everywhere, which is why combination approaches have shown their largest gains in this group rather than in exon 19 deletion.

## Sources

- TAGRISSO prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e81b4a7-b971-45e1-9c31-29cea8c87ce7

## Connected records

- 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 T790M](https://onco.cc/biomarkers/egfr-t790m/)
- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- drugs: [Afatinib](https://onco.cc/drugs/afatinib/), [Amivantamab](https://onco.cc/drugs/amivantamab/), [cobas EGFR Mutation Test v2](https://onco.cc/drugs/cobas-egfr-mutation-test/), [Dacomitinib](https://onco.cc/drugs/dacomitinib/), [Erlotinib](https://onco.cc/drugs/erlotinib/), [Gefitinib](https://onco.cc/drugs/gefitinib/), [Lazertinib](https://onco.cc/drugs/lazertinib/), [Osimertinib](https://onco.cc/drugs/osimertinib/)
- terms: [EGFR exon 19 deletion & L858R](https://onco.cc/terms/egfr-exon19-l858r/), [EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)](https://onco.cc/terms/egfr-mutation-subtypes/)
- key papers: [EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes](https://onco.cc/key-papers/paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019/), [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/)
- targets: [EGFR](https://onco.cc/targets/egfr/)

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