scholarly journals Differential significance of molecular subtypes which were classified into EGFR exon 19 deletion on the first line afatinib monotherapy

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Nahomi Tokudome ◽  
Yasuhiro Koh ◽  
Hiroaki Akamatsu ◽  
Daichi Fujimoto ◽  
Isamu Okamoto ◽  
...  
Keyword(s):  
Molecular Subtypes ◽  
First Line ◽  
Exon 19 Deletion ◽  
Exon 19

scholarly journals The Value of Next-Generation Sequencing for Treatment in Non-Small Cell Lung Cancer Patients: The Observational, Real-World Evidence in China

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Yan Zhang ◽  
Wen-Xiang Shen ◽  
Li-Na Zhou ◽  
Min Tang ◽  
Yue Tan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Real World ◽  
Somatic Mutations ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Exon 19 Deletion ◽  
Nsclc Patients ◽  
Generation Sequencing ◽  
Exon 19

Background. Great success has been made in the targeting therapy of advanced non-small cell lung cancer (NSCLC). Nowadays, next generation sequencing (NGS) is acquirable and affordable in developed area of China. Using this feasible and accurate method of detecting therapeutic genes would help to select optimal treatments to extend patients survival. Here, we identified somatic mutations by NGS and analyzed the value for treatment of NSCLC in a real-world clinical setting. Methods. NGS was carried out on biopsy samples obtained from 66 advanced unresectable NSCLC patients who had not received any treatment. 23 patients received liquid biopsy after failure of first-line targeted treatment. The mutation profiling as well as associations between mutations and clinicopathological characters was analyzed. The study also assessed the values of NGS for choosing treatment options and predicting prognosis in NSCLC patients. Results. 152 somatic mutations were identified in 45 (68.18%) tissue samples. The most frequently mutated genes were EGFR (42.42%), TP53 (31.82%) and KRAS (15.15%). Specifically, the most frequent EGFR mutation subtypes were exon 19 deletion (60.71%) and L858R in exon 21 (46.43%). 83.33% mutated patients received targeted therapy. Among the adenocarcinoma cases, patients with EGFR exon 19 deletion mutation have longer overall survival (OS) than the wide-type (36.0 months versus 19.0 months p=0.046). In addition, in the smoking group, patients with EGFR exon 19 deletion mutation tended to have longer OS (38.0 months versus 16.5 months p<0.01). After the failure of first-line targeted therapy, 23 EGFR mutated patients received liquid biopsy, and the positive rate of T790M mutation in EGFR exon 20 was 47.83%. T790M positive patients have longer progression-free survival (PFS) than the others (15 months versus 9.5 months p=0.025). Conclusions. The observational study from real-world demonstrated that using NGS in routine clinical detection may be useful in guiding the therapy decisions and benefit more Chinese NSCLC patients.

scholarly journals Patients Harboring Uncommon EGFR Exon 19 Deletion-insertion Mutations Respond Well to First-generation EGFR Inhibitors and Osimeritinib Upon Acquisition of T790M

2021 ◽  
Author(s):  
Yurong Wang ◽  
Ruipan Zheng ◽  
Peizhu Hu ◽  
Ziheng Zhang ◽  
Shujing Shen ◽  
...  
Keyword(s):  
First Generation ◽  
Resistance Mutation ◽  
Resistance Mechanisms ◽  
First Line ◽  
T790m Mutation ◽  
Similar Treatment ◽  
Significant Difference ◽  
Exon 19 Deletion ◽  
Egfr Tkis ◽  
Exon 19

Abstract Background: This study is to investigate the effects and resistance mechanisms of first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients carrying rare EGFR exon 19 deletion-insertion (19delins) mutations. Methods: The next generation sequencing (NGS) data of 1783 patients diagnosed as advanced NSCLC from November 2017 to September 2020 were successively and retrospectively reviewed. 41 patients with EGFR 19delins and 41 patients with EGFR exon 19 deletion (19del) were enrolled in this study, who were given first generation EGFR TKIs as first-line therapy. Results: 17 mutation types of EGFR 19delins were identified in this study, L747_P753delinsS (10/41) and L747_A750delinsP (9/41) were the most frequent mutation types, followed by L747_T751delinsP (6/41) and E746_S752delinsV (3/41). Under the same baseline characteristics, median progression-free survival (mPFS) was similar in patients with EGFR 19delins to those with EGFR 19del (10.4 months vs. 13.1 months, p=0.1076). Interestingly, patients with L747_T751delinsP had a better mPFS than those with other variants (18.7 months vs. 13.1 months, p=0.035). No significant difference in mPFS was found among the three groups of gefitinib, icotinib, and erlotinb with 14.7 months, 10.9 months, and 13.1 months (p>0.05). After progression from first-line EGFR TKIs, both EGFR 19delins and EGFR 19del had similar rates of developing resistance mechanisms including EGFR T790M mutation (45.8% vs. 57.8%). Patients acquiring T790M mutation received osimeritinib as second-line treatment, and the mPFS was similar between the groups of EGFR 19delins (n=8) and EGFR 19del (n=10): 12.0 months vs. 12.2 months (p=0.97). Conclusion: Our results indicate that patients with uncommon EGFR 19delins can also benefit from first-generation EGFR TKIs treatment, having similar treatment responses and survival outcomes to those with EGFR 19del, even similar clinical outcomes from osimeritinib upon acquiring T790M resistance mutation.

Multicenter prospective trial of customized erlotinib for advanced non-small cell lung cancer (NSCLC) patients (p) with epidermal growth factor receptor (EGFR) mutations: Final results of the Spanish Lung Cancer Group (SLCG) trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8023-8023
Author(s):  
B. Massuti ◽  
T. Morán ◽  
R. Porta ◽  
C. Queralt ◽  
F. Cardenal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Negative Impact ◽  
Cox Model ◽  
Prospective Trial ◽  
Complete Response ◽  
Egfr Mutations ◽  
First Line ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
Exon 19

8023 Background: The purpose of the study was to evaluate the efficacy of erlotinib and the feasibility of screening for EGFR mutations in advanced NSCLC p (chemonaive or relapsed after 2 prior chemotherapy regimens). Methods: Exon 19 deletions and L858R mutations in tumor and paired serum DNA were assessed in one central laboratory, using three different techniques. Results: From April 2005 to December 2008, 2507 p were screened. EGFR mutations were detected in 358 p; 217 were entered on the trial: 158 (72.8%) female; 148 (68.2%) never-smokers; 176 (81.1%) adenocarcinoma; 134 (62.3%) exon 19 deletion, 83 (37.7%) L858R mutation; 112 (51.6%) first-line, 104 (48.4%) second-line. Response in 139/197 evaluable p (70.6%); complete response (CR) in 24 p (12.2%). Odds ratio for response: 3 for p with exon 19 deletion (P=0.001). Time to progression (TTP): 14 months (m). Median survival (MS): 27 m. MS according to response shown in table. Cox model for TTP showed that male gender (hazard ratio [HR], 2.3; P=0.001), L858R mutation (HR, 1.8; P=0.008), and mutated EGFR in serum (HR,1.6; P=0.03) had a negative impact. Conclusions: A multicenter study of customized erlotinib, using a central screening laboratory, is feasible and shows the outstanding benefit to p for selecting erlotinib treatment based on EGFR mutation status. The SLCG has initiated a randomized trial of first-line erlotinib vs chemotherapy. [Table: see text] No significant financial relationships to disclose.

Efficacy of gefitinib in patients with advanced non-small cell carcinoma of the lung harboring common, uncommon and complex EGFR mutations

2021 ◽  
Vol 08 ◽  
Author(s):  
Wang Chun Kwok ◽  
Ka Yan Chiang ◽  
James Chung Man Ho ◽  
Terence Chi Chun Tam ◽  
Mary Sau Man Ip ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Small Cell ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
First Line Treatment ◽  
Exon 19

Background: As the commonest EGFR-TKI being used in Hong Kong, gefitinib has shown to be efficacious and safe as first line treatment for L858R mutation and exon 19 deletion with less gastrointestinal and cutaneous adverse events than erlotinib and afatinib. However, the evidence for therapeutic efficacy for uncommon and complex EGFR mutations is lacking. Whether gefitinib is efficacious for uncommon and complex EGFR mutations worth studying. Objectives: To assess the therapeutic efficacy of gefitinib, as measured by progression-free survival and overall survival, among advanced stage lung cancer patients with common, uncommon and complex EGFR mutations. Methods: This is a retrospective cohort study that included 241 Chinese patients with advanced non-small cell carcinoma of lung harboring EGFR mutations and received gefitinib 250 mg daily as first-line treatment. The progression-free survival [PFS] and overall survival [OS] for patients with different EGFR mutations, namely exon 19 deletion, L858R mutation in exon 21, uncommon EGFR mutations and complex EGFR mutations were analyzed. Results: Among the 241 patients, 118 [49%] had exon 19 deletion, 104 [43%] had L858R mutation in exon 21, 6 [2.5%] had uncommon EGFR mutations, 13 [5.4%] had complex EGFR mutations. The mean age was 69. 72% of the patients were female and with 81% being non-smoker. For patients with complex EGFR mutations, regardless of the presence of exon 19 deletion and L858R mutation as the component, have better PFS and OS than patients with single common EGFR mutations [Exon 19 deletion or L858R mutation]. Patients with uncommon EGFR mutations have inferior PFS and OS than those with common EGFR mutations. Conclusion: Gefitinib is a possible option for patients with complex EGFR mutations while it may not be the preferred treatment option in patients with single uncommon EGFR mutations.

Impact of Exon 19 Deletion Subtypes in EGFR-Mutant Metastatic Non–Small-Cell Lung Cancer Treated With First-Line Tyrosine Kinase Inhibitors

2019 ◽  
Vol 20 (2) ◽  
pp. 82-87 ◽  
Author(s):  
Sabrina Rossi ◽  
Luca Toschi ◽  
Giovanna Finocchiaro ◽  
Vincenzo Di Noia ◽  
Maria Bonomi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Exon 19 Deletion ◽  
Egfr Mutant ◽  
Exon 19

First-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC) by gefitinib

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19088-e19088
Author(s):  
V. Moiseyenko ◽  
S. A. Procenko ◽  
E. V. Levchenko ◽  
A. S. Barchuk ◽  
D. E. Matsko ◽  
...  
Keyword(s):  
Disease Progression ◽  
Egfr Mutation ◽  
Surgical Intervention ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Conventional Dose ◽  
Exon 19 Deletion ◽  
Ecog Ps ◽  
Tumor Dna ◽  
Exon 19

e19088 Background: Gefitinib shows outstandingly high rates of clinical benefit in NSCLC pts with EGFR mutation and is better tolerable than conventional chemotherapy, therefore its consideration for the upfront treatment is warranted. Methods: 21 chemonaive pts with inoperable NSCLC were selected based on the presence of EGFR mutation in the tumor DNA (16 exon 19 deletions and 5 T858G substitutions). All cases were adenocarcinomas; median age: 60 years (range: 36 - 81 years); males/females: 6/15; ECOG PS 0/1/2/3: 4/10/6/1. Gefitinib was administered at conventional dose 250 mg/d. Results: The overall disease control rate was 95% (CR: 2/21; PR: 11/21; SD: 7/21). Complete responses were observed only in tumors with exon 19 deletion, whereas the only patient with disease progression had codon 858 substitution. Grade III toxicity occurred only in 3 pts (2: skin rash; 1: diarrhea). Time to disease progression ranged from 2+ to 18 months. 3 pts achieved an operable status of the disease upon the treatment, and therefore were subjected to surgical intervention followed by adjuvant gefitinib therapy. Conclusions: Gefitinib may be considered as the treatment of choice for chemonaive EGFR mutation-containing inoperable NSCLC. No significant financial relationships to disclose.

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