Loading
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.
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.
In plain words · A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
L858R opens the same EGFR treatments as an exon 19 deletion: osimertinib, or amivantamab with lazertinib, as first treatment for advanced lung cancer, and osimertinib after surgery. Responses tend to be a little shorter than with exon 19 deletions, which is one reason your team may discuss adding chemotherapy.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
The EGFR exon 21 c.2573T>G (p.L858R) substitution detected by PCR or sequencing in tumour tissue or plasma.
“Exon 19 deletion or exon 21 L858R substitution mutation”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| EGFR exon 21 L858R (or exon 19 deletion) | Osimertinib | Non-small-cell lung cancer | FDA | label |
| EGFR exon 21 L858R (or exon 19 deletion) | Lazertinib | Non-small-cell lung cancer | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| cobas EGFR Mutation Test v2 | Roche Molecular Systems | Non-Small Cell Lung Cancer (NSCLC) - Tissue | Osimertinib | P120019/S007 (11/13/2015) |
| FoundationOne Liquid CDx | Foundation Medicine | Non-Small Cell Lung Cancer (NSCLC) - Plasma | OsimertinibErlotinibGefitinib | P190032 (08/26/2020) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
It shows that the driver frequencies quoted in Western guidelines are population statistics rather than facts about the disease, which matters for how many patients anywhere are expected to benefit from a given medicine.
It is the practical guide to what to do after transformation: treat it as small-cell lung cancer with platinum and etoposide, expect central nervous system disease, and do not expect a checkpoint inhibitor to help.
It is the document that defines what a complete lung cancer molecular report looks like, and its asymmetry about plasma, rule in but never rule out, is the single most useful sentence in it.
Shares EGFR exon 19 deletion, EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M), Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors, Amivantamab and the tags biomarker, egfr.
Shares EGFR T790M, EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M), Gefitinib, Erlotinib.
Shares Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors, Non-small-cell lung cancer and the tag biomarker.
Shares Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors, Non-small-cell lung cancer and the tag biomarker.
Shares Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors, Non-small-cell lung cancer and the tag biomarker.
Shares Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors, Non-small-cell lung cancer and the tag biomarker.
Shares EGFR T790M, Amivantamab, Non-small-cell lung cancer and the tag biomarker.
Shares EGFR exon 19 deletion, Non-small-cell lung cancer and the tag biomarker.