# 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

## Sources

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

## Connected records

- biomarkers: [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/)
- targets: [EGFR](https://onco.cc/targets/egfr/)

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JSON: https://onco.cc/api/v1/entities/egfr-l858r.json