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 1–50 of 69 evidence items across 3 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
High-Grade Glioma, NOS1
EGFR L858R	Erlotinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID4295 In an in vitro study, a Ba/F3 cell line expressing EGFR L858R demonstrated increased sensitivity to erlotinib treatment, compared to Ba/F3 cells expressing EGFR wild-type. Variant function was assesse… (full text at CIViC) PMID 17177598 · Lee et al., 2006 · Open in CIViC	civic
Lung Adenocarcinoma16
BRAF V600E AND EGFR L858R AND EGFR T790M	Osimertinib	Predictive	C	Supports Resistance	3	submitted	EID11098 A 42 year old man with non-smoking history presented with EGFR L858R positive lung adenocarcinoma. He was given various treatments including erlotinib and gefitinib and progressed four years later. bi… (full text at CIViC) PMID 29074209 ·

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 Non-Small Cell Carcinoma33
EGFR L858R	(prognostic)	Prognostic	B	Supports Better Outcome	3	accepted	EID347 Median survival of patients with EGFR L858R mutation is better than those with wild type EGFR. PMID 24662454 · Douillard et al., 2014 · Open in CIViC	civic
EGFR L858R	(oncogenic)	Oncogenic	B	Supports Oncogenicity	3	submitted	EID13027 In this study, EGFR L858R was identified in multiple lung non-small cell carcinoma (NSCLC) cohorts, including 1 of 10 gefitinib-sensitive tumors, 3 of 7 erlotinib-sensitive tumors, 5 of 15 untreated … (full text at CIViC) PMID 15329413 · Pao et al., 2004 · Open in CIViC	civic
EGFR L858R	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID13024 In this study, the authors identified a somatic EGFR L858R mutation in two patients with gefitinib-responsive non-small cell lung cancer. Functional analysis of EGFR L858R expressed in Cos-7 cells dem… (full text at CIViC) PMID 15118073 · Lynch et al., 2004 · Open in CIViC	civic
EGFR L858R	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID13026 In this preclinical study, biochemical and structural analyses demonstrated that the EGFR L858R kinase exhibited approximately 50-fold greater catalytic activity than wild-type EGFR and adopted a cons… (full text at CIViC) PMID 17349580 · Yun et al., 2007 · Open in CIViC	civic
EGFR L858R	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID13029 Expression of EGFR L858R in non-small cell lung cancer (NSCLC) cell lines (H1299 and CL1-0) significantly increased cell invasion compared with wild-type EGFR, whereas EGFR L858R-specific knockdown re… (full text at CIViC) PMID 26338423 · Tsai et al., 2015 · Open in CIViC	civic
EGFR L858R	(oncogenic)	Oncogenic	D	Supports Oncogenicity	3	submitted	EID13030 Expression of EGFR L858R in stable cell models resulted in increased phosphorylation of EGFR tyrosine residues Y845, Y992, and Y1068 compared with wild-type EGFR following EGF stimulation. In both sta… (full text at CIViC) PMID 15284455 · Sordella et al., 2004 · Open in CIViC	civic
EGFR L858R	Afatinib	Predictive	A	Supports Sensitivity Response	5	accepted	EID2997 Afatinib, an irreversible inhibitor of the ErbB family of tyrosine kinases has been approved in the US for the first-line treatment of patients with metastatic non-small-cell lung cancer (NSCLC) who h… (full text at CIViC) PMID 23982599 · Dungo et al., 2013 · Open in CIViC	civic
EGFR L858R	Afatinib	Predictive	C	Supports Sensitivity Response	—	submitted	EID2630 In a phase 2b/3 study of 585 stage IIIB-IV lung adenocarcinoma patients who had a previous round of EGFR-TKI treatment, archival material was available for 141 patients. EGFR mutational analysis revea… (full text at CIViC) PMID 22452896 · Miller et al., 2012 · Open in CIViC	civic
EGFR L858R	Afatinib	Predictive	D	Supports Sensitivity Response	2	accepted	EID968 Cells harboring L858R were sensitive to afatinib. This study performed drug response assays using five human NSCLC cell lines with various combinations of EGFR mutations. In order to directly compare … (full text at CIViC) PMID 26515464 · Hirano et al., 2015 · Open in CIViC	civic
EGFR L858R	Afatinib	Predictive	D	Supports Sensitivity Response	2	accepted	EID2629 In an in vitro study using NCI-H1666 cells (wildtype EGFR) and NCI-H3255 cells (EGFR-L858R), inhibition of cell growth was used as an assay to determine sensitivity to irreversible tyrosine kinase inh… (full text at CIViC) PMID 18408761 · Li et al., 2008 · Open in CIViC	civic
EGFR L858R	Canertinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID2631 In an in vitro study using NCI-H1666 cells (wildtype EGFR) and NCI-H3255 cells (EGFR-L858R), inhibition of cell growth was used as an assay to determine sensitivity to irreversible tyrosine kinase inh… (full text at CIViC) PMID 18408761 · Li et al., 2008 · Open in CIViC	civic
EGFR L858R	Crizotinib	Predictive	C	Supports Resistance	3	accepted	EID4288 This study analyzed patients with non small cell lung cancer (NSCLC) who were positive for EML4-ALK fusions (ALK+) and progressed on crizotinib monotherapy. One patient was biopsied twice following cr… (full text at CIViC) PMID 22235099 · Doebele et al., 2012 · Open in CIViC	civic
EGFR L858R	Dacomitinib	Predictive	B	Supports Sensitivity Response	5	accepted	EID4860 The authors pooled patients with exon 19 deletion and L858R EGFR (Exon 21) mutations from both studies (The ARCHER 1009 (NCT01360554) and A7471028 (NCT00769067)) to compare the efficacy of dacomitinib… (full text at CIViC) PMID 26768165 · Ramalingam et al., 2016 · Open in CIViC	civic
EGFR L858R	Dacomitinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID2627 In an in vitro study using NCI-H322 cells (wildtype EGFR) and NCI-H3255 cells (EGFR-L858R), inhibition of cell growth was used as an assay to determine sensitivity to irreversible tyrosine kinase inhi… (full text at CIViC) PMID 18089823 · Engelman et al., 2007 · Open in CIViC	civic
EGFR L858R	Durvalumab	Predictive	D	Supports Sensitivity Response	1	rejected	EID2633 EGFR L858R mutation has been associated with increased sensitivity to first generation EGFR tyrosine kinase inhibitors, including erlotinib and gefitinib.In an in vitro study using PC9 cells (EGFR L85… (full text at CIViC) PMID 24893891 · Cross et al., 2014 · Open in CIViC	civic
EGFR L858R	Erlotinib	Predictive	A	Supports Sensitivity Response	5	accepted	EID2994 On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib (Tarceva) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epider… (full text at CIViC) PMID 24868098 · Khozin et al., 2014 · Open in CIViC	civic
EGFR L858R	Erlotinib	Predictive	B	Supports Sensitivity Response	3	accepted	EID885 A randomized phase 3 trial (NCT00446225) involving 173 NSCLC patients with EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease. Patien… (full text at CIViC) PMID 22285168 · Rosell et al., 2012 · Open in CIViC	civic
EGFR L858R	Erlotinib	Predictive	C	Supports Sensitivity Response	2	accepted	EID2632 In a phase II trial for bronchioloalveolar carcinoma (BAC, or in situ pulmonary adenocarcinoma), EGFR exons 18-24 were analyzed in 7 patients who had shown a partial response to erlotinib. Two patient… (full text at CIViC) PMID 15329413 · Pao et al., 2004 · Open in CIViC	civic
EGFR L858R	Erlotinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID4265 MCF-7 cells were transduced with YFP tagged EGFR with E746_A750delELREA mutation, or YFP EGFR wildtype, and stained for ectopic YFP EGFR and phospho-Akt as a readout for EGFR pathway activity. Increas… (full text at CIViC) PMID 17877814 · de Gunst et al., 2007 · Open in CIViC	civic
EGFR L858R	Erlotinib	Predictive	D	Supports Sensitivity Response	2	accepted	EID4284 In an in vitro study using NCI-H1666 cells (wildtype EGFR) and NCI-H3255 cells (EGFR-L858R), inhibition of cell growth was used as an assay to determine sensitivity to reversible tyrosine kinase inhib… (full text at CIViC) PMID 18408761 · Li et al., 2008 · Open in CIViC	civic
EGFR L858R	Erlotinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID4286 In an in vitro study, Ba/F3 and NCI-H3255 cell lines expressing EGFR L858R demonstrated increased sensitivity to erlotinib treatment (IC50=0.006 and 0.068 µM). Sensitivity was determined by assessing … (full text at CIViC) PMID 24353160 · Yasuda et al., 2013 · Open in CIViC	civic
EGFR L858R	Erlotinib	Predictive	D	Supports Sensitivity Response	1	accepted	EID4287 In an in vitro study, CHO and NCI-H3255 cells expressing EGFR L858R mutation were associated with sensitivity to erlotinib treatment. Sensitivity was determined by assessing cell density. PMID 27612423 · Ray et al., 2016 · Open in CIViC	civic
EGFR L858R	Gefitinib	Predictive	B	Supports Sensitivity Response	3	accepted	EID1665 90 NSCLC patients with stage IIIB/IV chemotherapy-resistant tumors were treated with gefitinib, and the L858R EGFR mutation was associated with longer time to treatment failure than those with wild-ty… (full text at CIViC) PMID 18509184 · Yang et al., 2008 · Open in CIViC	civic
EGFR L858R	Gefitinib	Predictive	B	Supports Sensitivity Response	4	accepted	EID2621 In a phase 3 clinical trial of non-small cell lung cancer (NSCLC) patients, a subset of patients with EGFR mutations (n=44) treated with gefitinib were associated with improved progression free surviv… (full text at CIViC) PMID 20038723 · Douillard et al., 2010 · Open in CIViC	civic
EGFR L858R	Gefitinib	Predictive	C	Supports Sensitivity Response	—	submitted	EID2623 In a phase 3 clinical trial of Japanese NSCLC patients with EGFR mutations (n=230), patients treated with gefitinib were associated with improved progression free survival (10.8 months vs 5.4 months, … (full text at CIViC) PMID 20573926 · Maemondo et al., 2010 · Open in CIViC	civic
EGFR L858R	Gefitinib	Predictive	D	Supports Sensitivity Response	4	accepted	EID276 Gefinitib has been shown to be effective in treating cell lines with L858R missense mutations. PMID 15118125 · Paez et al., 2004 · Open in CIViC	civic
EGFR L858R	Erlotinib + GefitinibSubstitutes	Predictive	B	Supports Sensitivity Response	3	accepted	EID229 There is no statistical difference in progression free survival between lung cancer patients treated with gefitinib or erlotinib with EGFR L858R mutations (N=72/242; univariate: P=0.283; multivariate:… (full text at CIViC) PMID 24736073 · Lim et al., 2014 · Open in CIViC	civic
EGFR L858R	Erlotinib + GefitinibSubstitutes	Predictive	B	Supports Sensitivity Response	4	accepted	EID275 In NSCLC patients treated with EGFR tyrosine kinase inhibitors, the presence of L858R mutation is prognostic for better progression free survival. PMID 24457318 · Fukihara et al., 2014 · Open in CIViC	civic
EGFR L858R	Afatinib + Erlotinib + GefitinibSubstitutes	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID12203 The goal of this study was to assess the frequency, overall survival, and classifying actionability of EGFR mutations in NSCLC within the Dutch population from 2013-2017. This study found that despite… (full text at CIViC) PMID 34298851 · Koopman et al., 2021 · Open in CIViC	civic
EGFR L858R	Lapatinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID2626 In an in vitro study using NCI-H1666 cells (wildtype EGFR) and NCI-H3255 cells (EGFR-L858R), inhibition of cell growth was used as an assay to determine sensitivity to reversible tyrosine kinase inhib… (full text at CIViC) PMID 18408761 · Li et al., 2008 · Open in CIViC	civic
EGFR L858R	Neratinib	Predictive	D	Supports Sensitivity Response	3	accepted	EID2628 In an in vitro study using NCI-H3255 cells (EGFR L858R), inhibition of cell growth was used as an assay to determine sensitivity to tyrosine kinase inhibitor (TKI) drugs. Cells with an EGFR L858R muta… (full text at CIViC) PMID 16818618 · Shimamura et al., 2006 · Open in CIViC	civic
EGFR L858R	Osimertinib	Predictive	D	Supports Sensitivity Response	2	accepted	EID4294 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
EGFR L858R AND EGFR T790M	Osimertinib	Predictive	A	Supports Sensitivity Response	4	accepted	EID11599 This phase 3 trial (NCT02151981) involved 419 patients with EGFR T790M mutant NSCLC who progressed after first-line EGFR inhibitor therapy (gefitinib, erlotinib, or afatinib) and were either treated w… (full text at CIViC) PMID 27959700 · Mok et al., 2017 · Open in CIViC	civic

Lung Non-Small Cell Carcinoma33

EGFR L858R

(prognostic)

Prognostic

Supports Better Outcome

accepted

EID347

Median survival of patients with EGFR L858R mutation is better than those with wild type EGFR.

PMID 24662454 · Douillard et al., 2014 · Open in CIViC