Variant · Snv

EGFR L858R

CI-VAR-00002436Explore in graph →NP_005219.2:p.Leu858ArgNM_005228.4:c.2573T>GClinVar 16609 CIViC 33 rs121434568

Curated evidence

Evidence by cancer (69 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 51–69 of 69 evidence items across 4 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Lung Non-Small Cell Carcinoma14
EGFR L858R AND MET Amplification	Capmatinib + GefitinibCombination	Predictive	C	Supports Sensitivity Response	3	submitted	EID11408 A 73-year old male (non-smoker) with advanced non-small-cell lung cancer (NSCLC) was found to have EGFR L858R mutation and MET amplification. The patient had a dramatic response to erlotinib and crizo… (full text at CIViC) PMID 31864558 · Gainor et al., 2020 · Open in CIViC	civic
EGFR L858R OR EGFR Exon 19 Deletion	Amivantamab + Carboplatin + PemetrexedCombination	Predictive	A	Supports Sensitivity Response	4	accepted	EID12156 In this phase III trial, 657 patients with locally advanced or metastatic NSCLC (Non-Small Cell Lung Cancer) harbouring EGFR mutations (exon 19 deletions or L858R) were treated with amivantamab plus c…

ClinVar

Clinical significance (1)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

clinvarCurated1 interpretation · review status and star rating as assigned by ClinVar.

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
16609	drug response	reviewed by expert panel	3	Adenocarcinoma of lung, response to tyrosine kinase inhibitor in, somatic; Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in, somatic; Tyrosine kinase inhibitor response; gefitinib response - Efficacy; Lung adenocarcinoma; Non-small cell lung carcinoma; Lung carcinoma; Neoplasm; Hereditary cancer-predisposing syndrome	germline/somatic

Lung Small Cell Carcinoma1
EGFR L858R	Erlotinib	Predictive	D	Supports Sensitivity Response	2	accepted	EID4293 In an in vitro study using NCI-H3255 cells (EGFR L858R mutation), inhibition of EGFR phosphorylation was used as an assay to determine sensitivity to EGFR tyrosine kinase inhibitors. NCI-H3255 cells d… (full text at CIViC) PMID 24893891 · Cross et al., 2014 · Open in CIViC	civic

Lung Small Cell Carcinoma1

EGFR L858R

Erlotinib

Predictive

Supports Sensitivity Response

accepted

EID4293

In an in vitro study using NCI-H3255 cells (EGFR L858R mutation), inhibition of EGFR phosphorylation was used as an assay to determine sensitivity to EGFR tyrosine kinase inhibitors. NCI-H3255 cells d… (full text at CIViC)

PMID 24893891 · Cross et al., 2014 · Open in CIViC

civic

Malignant Lung Neoplasm1
EGFR L858R AND EGFR T790M	Nano TACs	Predictive	D	Supports Sensitivity Response	3	submitted	EID13326 NanoTACs are peptide-derived PROTAC nanoparticles designed to target wild-type EGFR and the EGFR L858R/T790M variant. Unlike conventional tyrosine kinase inhibitors (TKIs), which temporarily inhibit E… (full text at CIViC) PMID 41386736 · Jeong et al., 2026 · Open in CIViC	civic

Malignant Lung Neoplasm1

EGFR L858R AND EGFR T790M

Nano TACs

Predictive

Supports Sensitivity Response

submitted

EID13326

NanoTACs are peptide-derived PROTAC nanoparticles designed to target wild-type EGFR and the EGFR L858R/T790M variant. Unlike conventional tyrosine kinase inhibitors (TKIs), which temporarily inhibit E… (full text at CIViC)

PMID 41386736 · Jeong et al., 2026 · Open in CIViC

civic

Malignant Neoplasm3
EGFR L858R	Erlotinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID5922 In an in vitro study performed after identification of the mutation in a malignant peritoneal mesothelioma patient, COS-7 cells expressing EGFR L858R demonstrated increased EGFR phosphotyrosine after … (full text at CIViC) PMID 20942962 · Foster et al., 2010 · Open in CIViC	civic
EGFR L858R	Dacomitinib + ErlotinibSubstitutes	Predictive	D	Supports Sensitivity Response	2	accepted	EID4285 In an in vitro study, a MCF-7 cell line expressing EGFR L858R mutation demonstrated sensitivity to erlotinib or dacomitinib (PF00299804) treatment, compared to MCF-7 cells expressing EGFR wild-type. S… (full text at CIViC) PMID 21132006 · Harada et al., 2011 · Open in CIViC	civic
EGFR L858R	Erlotinib + Gefitinib + Multikinase Inhibitor AEE788Substitutes	Predictive	D	Supports Sensitivity Response	3	accepted	EID3811 EGFR L858R was expressed in Ba/F3 cells which do not contain endogenous EGFR, and conferred growth factor independance to the cells. Cells were plated and treated with 1st generation EGFR inhibitors G… (full text at CIViC) PMID 19147750 · Kancha et al., 2009 · Open in CIViC	civic

Malignant Neoplasm3

EGFR L858R

Erlotinib

Predictive

Supports Sensitivity Response

accepted

EID5922

In an in vitro study performed after identification of the mutation in a malignant peritoneal mesothelioma patient, COS-7 cells expressing EGFR L858R demonstrated increased EGFR phosphotyrosine after … (full text at CIViC)

PMID 20942962 · Foster et al., 2010 · Open in CIViC

civic

EGFR L858R

Dacomitinib + ErlotinibSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID4285

In an in vitro study, a MCF-7 cell line expressing EGFR L858R mutation demonstrated sensitivity to erlotinib or dacomitinib (PF00299804) treatment, compared to MCF-7 cells expressing EGFR wild-type. S… (full text at CIViC)

PMID 21132006 · Harada et al., 2011 · Open in CIViC

civic

EGFR L858R

Erlotinib + Gefitinib + Multikinase Inhibitor AEE788Substitutes

Predictive

Supports Sensitivity Response

accepted

EID3811

EGFR L858R was expressed in Ba/F3 cells which do not contain endogenous EGFR, and conferred growth factor independance to the cells. Cells were plated and treated with 1st generation EGFR inhibitors G… (full text at CIViC)

PMID 19147750 · Kancha et al., 2009 · Open in CIViC

civic