{"entity":{"id":"egfr-l858r","kind":"biomarker","name":"EGFR L858R","aka":["L858R","EGFR exon 21 L858R","exon 21 substitution","EGFR L858R mutation","p.L858R"],"tldr":"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.","asOf":"2026-09-23","links":[{"label":"TAGRISSO prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e81b4a7-b971-45e1-9c31-29cea8c87ce7"}],"tags":["biomarker","egfr"],"related":["egfr-exon-19-deletion","egfr-t790m"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":["osimertinib","erlotinib","gefitinib","afatinib","dacomitinib","amivantamab","lazertinib","cobas-egfr-mutation-test"],"companies":[],"institutions":[],"pathways":[],"terms":["egfr-exon19-l858r","egfr-mutation-subtypes"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"egfr","measurement":"sequencing-variant","scoringRule":{"text":"The EGFR exon 21 c.2573T>G (p.L858R) substitution detected by PCR or sequencing in tumour tissue or plasma.","quote":"Exon 19 deletion or exon 21 L858R substitution mutation","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","sourceLabel":"FDA: List of FDA-Authorized Companion Diagnostic Devices"},"thresholds":[{"value":"EGFR exon 21 L858R (or exon 19 deletion)","drugId":"osimertinib","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e81b4a7-b971-45e1-9c31-29cea8c87ce7","quote":"whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.","status":"current"},{"value":"EGFR exon 21 L858R (or exon 19 deletion)","drugId":"lazertinib","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c417f9ee-2027-4ed5-92ad-3c19266de16c","quote":"LAZCLUZE, in combination with amivantamab, is indicated for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test","status":"current"}],"tests":["foundationone-cdx","foundationone-liquid-cdx","guardant360-cdx","tempus-xt","trusight-oncology-comprehensive"],"assays":["egfr-cobas-v2","egfr-therascreen","oncomine-dx"],"companionDiagnostics":[{"device":"cobas EGFR Mutation Test v2","maker":"Roche Molecular Systems","drugs":["osimertinib"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Tissue","pma":"P120019/S007 (11/13/2015)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"FoundationOne Liquid CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["osimertinib","erlotinib","gefitinib"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Plasma","pma":"P190032 (08/26/2020)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"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."},"route":"/biomarkers/egfr-l858r/","neighbours":{"biomarker":[{"id":"egfr-exon-19-deletion","kind":"biomarker","name":"EGFR exon 19 deletion","route":"/biomarkers/egfr-exon-19-deletion/"},{"id":"egfr-t790m","kind":"biomarker","name":"EGFR T790M","route":"/biomarkers/egfr-t790m/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"drug":[{"id":"afatinib","kind":"drug","name":"Afatinib","route":"/drugs/afatinib/"},{"id":"amivantamab","kind":"drug","name":"Amivantamab","route":"/drugs/amivantamab/"},{"id":"cobas-egfr-mutation-test","kind":"drug","name":"cobas EGFR Mutation Test v2","route":"/drugs/cobas-egfr-mutation-test/"},{"id":"dacomitinib","kind":"drug","name":"Dacomitinib","route":"/drugs/dacomitinib/"},{"id":"erlotinib","kind":"drug","name":"Erlotinib","route":"/drugs/erlotinib/"},{"id":"gefitinib","kind":"drug","name":"Gefitinib","route":"/drugs/gefitinib/"},{"id":"lazertinib","kind":"drug","name":"Lazertinib","route":"/drugs/lazertinib/"},{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/"}],"term":[{"id":"egfr-exon19-l858r","kind":"term","name":"EGFR exon 19 deletion & L858R","route":"/terms/egfr-exon19-l858r/"},{"id":"egfr-mutation-subtypes","kind":"term","name":"EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)","route":"/terms/egfr-mutation-subtypes/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}]}}