|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
On July 13, 2015, the FDA approved gefitinib (Iressa; AstraZeneca UK Limited) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.
|
26980062 |
2016 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
One hundred and eight patients harbored L858R mutation in their tumors and 80 patients provided serial blood samples as pre-planned scheduled.
|
27619632 |
2016 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
With clinical CTC samples, we then show that the isolated single CTCs are representative of dominant EGFR mutations such as T790M and L858R found in the primary tumor.
|
26924553 |
2016 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Thirty-five LADC patients who received epidermal growth factor receptor (EGFR)-TKI therapy, including ten who received tumor rebiopsy after development of resistance, were subjected to picoliter-ddPCR-cfDNA analysis to determine the fraction of cfDNA with TKI-sensitive (L858R and inflame exon 19 deletions) and -resistant (i.e., T790M) mutations, as well as their concordance with mutation status in rebiopsied tumor tissues.
|
26768482 |
2016 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Next-generation sequencing (NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858R mutations.
|
27001083 |
2016 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Of a total 58 baseline cell-free DNA (cfDNA) samples available for ddPCR analysis, 43 (74.1%) had the same mutation in the matched tumors (clinical sensitivity: 70.8% [17/24] for L858R and 76.5% [26/34] for ex19del).
|
26755650 |
2016 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
EGFR mutation status was retrospectively determined for 76 patients, 52 (68.4%) of whom had EGFR-mutated tumors (exon 19 deletions in 26 and L858R point mutation in 24).
|
26725183 |
2016 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
There was high agreement for activating mutations between baseline cfDNA and tumor samples, especially for L858R mutation (kappa index = 0.679; p = 0.001).
|
27473086 |
2016 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Moreover, oral administration of AZD9291 as a single agent induced tumor regression in vivo in a H1975 tumor xenograft model and reduced EGFR(L858R/T790M) protein levels in xenograft tumors.
|
27044261 |
2016 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Expert consensus has defined minimum requirements for routine testing and identification of epidermal growth factor (EGFR) mutations (15% of tumors harbor EGFR exon 19 deletions or exon 21 L858R substitutions) and anaplastic lymphoma kinase (ALK) rearrangements (5% of tumors) in advanced lung adenocarcinomas (ACs).
|
26620497 |
2016 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Recently, overall survival benefit in patients with Del19- but not L858R-mutated tumors has been demonstrated after treatment with afatinib, an irreversible ErbB family blocker.
|
25629371 |
2015 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Univariate analyses of patients with EGFR mutations in cfDNA identified the L858R mutation in tumor tissue or in cfDNA as a marker of shorter OS (hazard ratio [HR], 2.70 [95% CI, 1.60-4.56]; P < .001) and PFS (HR, 2.04 [95% CI, 1.20-3.48]; P = .008).
|
26181014 |
2015 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
IHC was performed using mutation-specific antibodies for E746-A750 deletion (DEL) and L858R point mutation (L858R) in biopsies and tissue microarrays of resected tumors from 154 patients with pulmonary adenocarcinoma.
|
25687872 |
2015 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
A total of 72 patients were enrolled in this study, of which 62 patients (86.1%) had EGFR-mutant tumors (34 patients with exon 19 deletions, and 28 patients with L858R).
|
25514801 |
2015 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
To evaluate the clinical application of a new mutation-specific mouse monoclonal antibody for EGFR (L858R), we performed immunohistochemistry (IHC) studies with tumor samples from primary lung adenocarcinoma in retrospective and validation settings.
|
25286755 |
2015 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
However, whether there are some differences between those 2 groups in baseline clinical characteristics is still unclear.We enrolled consecutive 1271 NSCLC patients detected with either 19 Del or L858R and collected their baseline clinical characteristics including age, sex, comorbidity, smoking and drinking status, body mass index (BMI), TNM stage, histologic type, differentiation, tumor maximum diameter (TMD), and CEA level.
|
26554801 |
2015 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
For tumors with exon 19 deletions, the benefit was 50% greater (HR, 0.24; 95% CI, 0.20 to 0.29) than for tumors with exon 21 L858R substitution (HR, 0.48; 95% CI, 0.39 to 0.58; Pinteraction < .001).
|
25897154 |
2015 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
The tumor was found to harbor both EGFR L858R and ERBB2 S310F alterations and also tested positive for a known TP53 germline mutation.
|
24835218 |
2014 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions) make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs.
|
25296354 |
2014 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib (Tarceva, Astellas Pharma Inc., Northbrook, IL, http://www.us.astellas.com/) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.
|
24868098 |
2014 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
We report here a case of pulmonary adenocarcinoma with concomitant EGFR mutation in exon 21 (L858R) and ALK rearrangement in naive and relapsed tumors.
|
25312989 |
2014 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Eighteen out of 20 large cell carcinomas, not otherwise specified, had glandular differentiation upon immunohistochemistry, with an exon 21 L858R EGFR mutation in one (5 %) tumor, an exon 2 KRAS mutation in eight (40 %) tumors, and an ALK translocation in one (5 %) tumor, whereas two tumors positive for CK7 and CK5/6 and negative for all other markers were considered adenocarcinoma.
|
24221342 |
2014 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Of all the compounds tested, compound 3 displayed the best efficacy in EGFR(L858R/T790M)-driven tumors.
|
24723450 |
2014 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Consequently, 12 available tumor specimens (five specimens for delE746-A750 and seven specimens for L858R) with both factors were evaluated.
|
23645738 |
2013 |
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
EGFR mutations were detected in tumor tissues from 27 of 49 NSCLC patients of Han ethnic group , with a positive rate of 55.1%; 19 of them had exon 19 deletions, seven (7) had L858R point mutations in exon 21 of EGFR and one (1) had mutations in both exon 18 G719X and exon 20 T790M of EGFR.
|
23803047 |
2013 |