scholarly journals The percentage of Epidermal Growth Factor Receptor (EGFR)-mutated neoplastic cells correlates to response to tyrosine kinase inhibitors in lung adenocarcinoma

PLoS ONE ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. e0177822 ◽  
Author(s):  
Dario de Biase ◽  
Giovenzio Genestreti ◽  
Michela Visani ◽  
Giorgia Acquaviva ◽  
Monica Di Battista ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Egfr Mutated

scholarly journals Comparison of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung adenocarcinoma harboring different epidermal growth factor receptor mutation types

2020 ◽  
Author(s):  
Sojung Park ◽  
Sung Yong Lee ◽  
Dojin Kim ◽  
Yun Su Sim ◽  
Jeong-Seon Ryu ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Egfr Tkis

Abstract Background: Epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation types are associated with efficacy of EGFR TKIs. We investigated the clinical outcomes of afatinib, erlotinib, and gefitinib according to EGFR mutation type in patients with lung adenocarcinoma.Methods: Between May 2010 and December 2018, we investigated 363 patients with advanced lung adenocarcinoma harboring EGFR mutations who received EGFR TKIs. Efficacies of EGFR TKIs such as response rate, progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated according to exon 19 deletion (E19del), L858R point mutation (L858R) and uncommon mutations. Results: The frequency of E19del was 48.2%, that of L858R was 42.4%, and that of uncommon mutations was 9.4%. E19del and L858R were associated with superior PFS and OS compared with uncommon mutations. Erlotinib showed significantly inferior OS than other TKIs (30.8 ± 3.3 in erlotinib vs. 39.1 ± 4.3 in afatinib vs. 48.4 ± 6.3 in gefitinib; p = 0.031) in patients with L858R. Gefitinib showed significantly inferior PFS (4.6 ± 1.1 in gefitinib vs. 11.6 ± 2.7 in afatinib vs. 10.6 ± 2.7 in erlotinib; p = 0.049) in patients with uncommon mutations. Conclusion: Afatinib was significantly associated with a longer PFS, presenting constant effectiveness in all EGFR mutation types. Caution may be needed on the use of erlotinib for L858R and the use of gefitinib for uncommon EGFR mutations.

scholarly journals Systemic Inflammation Index and Tumor Glycolytic Heterogeneity Help Risk Stratify Patients with Advanced Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Treated with Tyrosine Kinase Inhibitor Therapy

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 309
Author(s):  
Kun-Han Lue ◽  
Chun-Hou Huang ◽  
Tsung-Cheng Hsieh ◽  
Shu-Hsin Liu ◽  
Yi-Feng Wu ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Lung Adenocarcinoma ◽  
Systemic Inflammation ◽  
Smoking Status ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Egfr Mutated

Tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with advanced epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma. Over half of patients failed to achieve prolonged survival benefits from TKI therapy. Awareness of a reliable prognostic tool may provide a valuable direction for tailoring individual treatments. We explored the prognostic power of the combination of systemic inflammation markers and tumor glycolytic heterogeneity to stratify patients in this clinical setting. One hundred and five patients with advanced EGFR-mutated lung adenocarcinoma treated with TKIs were retrospectively analyzed. Hematological variables as inflammation-induced biomarkers were collected, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation index (SII). First-order entropy, as a marker of heterogeneity within the primary lung tumor, was obtained by analyzing 18F-fluorodeoxyglucose positron emission tomography images. In a univariate Cox regression analysis, sex, smoking status, NLR, LMR, PLR, SII, and entropy were associated with progression-free survival (PFS) and overall survival (OS). After adjusting for confounders in the multivariate analysis, smoking status, SII, and entropy, remained independent prognostic factors for PFS and OS. Integrating SII and entropy with smoking status represented a valuable prognostic scoring tool for improving the risk stratification of patients. The integrative model achieved a Harrell’s C-index of 0.687 and 0.721 in predicting PFS and OS, respectively, outperforming the traditional TNM staging system (0.527 for PFS and 0.539 for OS, both p < 0.001). This risk-scoring model may be clinically helpful in tailoring treatment strategies for patients with advanced EGFR-mutated lung adenocarcinoma.

scholarly journals Efficacy of Next-Generation EGFR-TKIs in Patients With Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 19 ◽  
pp. 153303382094042
Author(s):  
Yi-Tian Qi ◽  
Yi Hou ◽  
Liang-Chen Qi
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Receptor Tyrosine Kinase Inhibitors

Background: The efficacy of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer who have failed first-generation epidermal growth factor receptor-tyrosine kinase inhibitors still remains under investigation. Objective: The aim of this meta-analysis was to systematically assess the efficacy and safety profiles of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer who failed first-generation epidermal growth factor receptor-tyrosine kinase inhibitors. Methods: We performed a comprehensive search of several electronic databases up to September 2018 to identify clinical trials. The primary end point was overall survival, progression-free survival, disease controlled rate, objective response rate, and adverse events. Epidermal growth factor receptor-tyrosine kinase inhibitor emergent severe adverse events (grade ≥ 3) were analyzed. Odds ratio along with 95% confidence interval were utilized for main outcome analysis. Results: In total, we had 3 randomized controlled trials in this analysis. The group of next-generation epidermal growth factor receptor-tyrosine kinase inhibitors had significantly improved progression-free survival (odds ratio = 0.34, 95% confidence interval = 0.29-0.40, P < .00001), as well as objective response rate (odds ratio = 10.48, 95% confidence interval = 3.87-28.34, P < .00001) and disease controlled rate (odds ratio = 6.03, 95% confidence interval = 4.41-8.25, P < .00001). However, there was no significant difference in overall survival with next-generation epidermal growth factor receptor-tyrosine kinase inhibitors (odds ratio = 1.05, 95% confidence interval = 0.85-1.31, P = .66). Meanwhile, the odds ratio for treatment-emergent severe adverse events (diarrhea, rash/acne, nausea, vomiting, anemia) between patients who received next-generation epidermal growth factor receptor-tyrosine kinase inhibitors and those who received first-generation epidermal growth factor receptor-tyrosine kinase inhibitors did not show safety benefit ( P > .05). Conclusions: Next-generation epidermal growth factor receptor-tyrosine kinase inhibitors were shown to be the better agent to achieve higher response rate and longer progression-free survival in patients with non-small cell lung cancer as the later-line therapy for previously treated patients with first-generation epidermal growth factor receptor-tyrosine kinase inhibitors. Meanwhile, they did not achieve benefit in overall survival and safety compared with the chemotherapy group. Further research is needed to develop a database of all EGFR mutations and their individual impacts on the various treatments.

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