Lung Non-Small Cell Carcinoma

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

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

In this preclinical study, expression of EGFR L858R in Ba/F3 cells induced interleukin-3-independent proliferation, demonstrating ligand-independent cellular transformation. EGFR L858R was constitutiv… (full text at CIViC)

PMID 16204070 · Jiang et al., 2005 · Open in CIViC

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

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

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

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

A phase III clinical trial (NCT00949650) found that median progression free survival among patients with exon 19 deletions or L858R EGFR mutations (n = 308) was 13.6 months for afatinib and 6.9 months… (full text at CIViC)

PMID 23816960 · Sequist et al., 2013 · Open in CIViC

Afatinib is an irreversible covalent inhibitor of EGFR (second generation). This Phase III clinical trial (LUX-Lung 6; NCT01121393) was performed in Asian patients with EGFR mutant advanced NSCLC. 364… (full text at CIViC)

PMID 24439929 · Wu et al., 2014 · Open in CIViC

In a phase 2 study of patients with lung adenocarcinoma (stage IIIb with pleural effusion or stage IV) and EGFR mutations, treated with afatinib were assessed by objective response. 129 patients were … (full text at CIViC)

PMID 22452895 · Yang et al., 2012 · Open in CIViC

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

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

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

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

In an in vitro study, Ba/F3 cell line expressing EGFR L858R did not show sensitivity to cetuximab treatment, while cells expressing EGFR-RAD51 fusion were sensitive. Sensitivity was determined by asse… (full text at CIViC)

PMID 27102076 · Konduri et al., 2016 · Open in CIViC

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

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

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

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

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

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

In a prospective study of 46 Caucasian, advanced lung adenocarcinoma patients harboring EGFR mutations, first-line erlotinib treatment was assessed. Average PFS and OS for these 46 patients was 11 mon… (full text at CIViC)

PMID 27032107 · De Grève et al., 2016 · Open in CIViC

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

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

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

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

In an in vitro study, Ba/F3 cell line expressing EGFR L858R was associated with sensitivity to erlotinib treatment (IC50 26.9 ± 12.4nM). EGFR L858R was used as a positive control for comparing sensiti… (full text at CIViC)

PMID 27102076 · Konduri et al., 2016 · Open in CIViC

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

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

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

In a phase 3 clinical trial of Korean, never-smoker, lung adenocarcinoma patients, a subset of patients with EGFR mutations (n=42) treated with gefitinib were associated with improved overall response… (full text at CIViC)

PMID 22370314 · Han et al., 2012 · Open in CIViC

In a Japanese Phase III clinical trial, noninferiority of Gefitinib as compared to Erlotinib was assessed in 561 postoperative recurrent or stage IIIb/VI patients who had undergone prior chemotherapy … (full text at CIViC)

PMID 27022112 · Urata et al., 2016 · Open in CIViC

Mutational profiling was performed on EGFR exons 18-24 from a group of 10 retrospectively chosen patients who had shown partial response or clinical improvement in response to gefitinib. Of 7 tumors w… (full text at CIViC)

PMID 15329413 · Pao et al., 2004 · Open in CIViC

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

Gefinitib has been shown to be effective in treating cell lines with L858R missense mutations.

PMID 15118125 · Paez et al., 2004 · Open in CIViC

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

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

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

A 67 year old female with stage IIIA lung adenocarcinoma had right lobectomy followed by 4 cycles adjuvant chemotherapy with pemetrexed and cisplatin. Next generation sequencing found EGFR L858R mutat… (full text at CIViC)

PMID 35004270 · Wang et al., 2021 · Open in CIViC

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

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

A 62 year old patient with 4 pack-year smoking history with back and flank pain was found to have metastatic lung adenocarcinoma by CT and MRI. Targeted NGS sequencing discovered an EGFR L858R mutatio… (full text at CIViC)

PMID 32193290 · Starrett et al., 2020 · Open in CIViC

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

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

A 76-year old woman (non-smoker) presented with stage IVB ling adenocarcinoma. Genetic testing was positive for EGFR L858R and T790M and osimertinib was given. Partial response was noted until progres… (full text at CIViC)

PMID 36313664 · Takamori et al., 2022 · Open in CIViC

A 67 year old female with stage IIIA lung adenocarcinoma had right lobectomy followed by 4 cycles adjuvant chemotherapy with pemetrexed and cisplatin. Next generation sequencing (NGS) found EGFR L858R… (full text at CIViC)

PMID 35004270 · Wang et al., 2021 · Open in CIViC

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

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… (full text at CIViC)

PMID 37879444 · Passaro et al., 2024 · Open in CIViC

In this trial (MARIPOSA), 1074 patients with Non-Small Cell Lung Cancer harbouring exon 19 deletion or exon 21 L858R substitution were randomized (2:2:1) to receive lazertinib-amivantamab (n=429), osi… (full text at CIViC)

PMID 38942080 · Felip et al., 2024 · Open in CIViC