Jenn-Yu Wu1, Chong-Jen Yu2, Jin-Yuan Shih3. 1. Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan. 2. Department of Internal Medicine, National Taiwan University Hospital, and College of Medicine, National Taiwan University, Taipei, Taiwan. 3. Department of Internal Medicine, National Taiwan University Hospital, and College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: jyshih@ntu.edu.tw.
Abstract
BACKGROUND: Two main categories of epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) patients are deletions in exon 19 and L858R in exon 21. Treatments of advanced NSCLC patients with these mutations are well documented, and clinical responses to tyrosine kinase inhibitors (TKIs) are favorable. However, effective treatments for patients with exon 20 insertion mutations are not well verified. We investigated the clinical response to various treatments (chemotherapy and TKIs) of advanced NSCLC patients with EGFR exon 20 insertions. PATIENTS AND METHODS: In this study, specimens from 3805 NSCLC patients were examined for EGFR mutations. Different first-line treatments and their effectiveness in NSCLC patients with exon 20 insertion EGFR mutations were investigated. RESULTS: In the cohort of the 3805 patients, 2112 (55.5%) had EGFR mutations, including 84 patients (4.0%) with exon 20 insertion mutations. Efficacy of different first-line chemotherapy or TKIs were evaluated. Pemetrexed-containing therapies were related to better progression-free survival (6.2 vs. 2.7 months; P < .001) and overall survival (28.0 vs. 15.4 months; P = .009) than regimens without pemetrexed. Patients with exon 20 insertions had a poor response to TKIs. However, the mutation Ala763_Tyr764insPheGlnGluAla (A763_Y764 insFQEA) was related to a favorable response to TKIs. CONCLUSION: Exon 20 insertion EGFR mutations comprised a considerable group of the entire population of patients with EGFR mutations. Different first-line treatments and variants of the exon 20 insertions might be related to different outcomes in advanced NSCLC patients.
BACKGROUND: Two main categories of epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) patients are deletions in exon 19 and L858R in exon 21. Treatments of advanced NSCLCpatients with these mutations are well documented, and clinical responses to tyrosine kinase inhibitors (TKIs) are favorable. However, effective treatments for patients with exon 20 insertion mutations are not well verified. We investigated the clinical response to various treatments (chemotherapy and TKIs) of advanced NSCLCpatients with EGFR exon 20 insertions. PATIENTS AND METHODS: In this study, specimens from 3805 NSCLCpatients were examined for EGFR mutations. Different first-line treatments and their effectiveness in NSCLCpatients with exon 20 insertion EGFR mutations were investigated. RESULTS: In the cohort of the 3805 patients, 2112 (55.5%) had EGFR mutations, including 84 patients (4.0%) with exon 20 insertion mutations. Efficacy of different first-line chemotherapy or TKIs were evaluated. Pemetrexed-containing therapies were related to better progression-free survival (6.2 vs. 2.7 months; P < .001) and overall survival (28.0 vs. 15.4 months; P = .009) than regimens without pemetrexed. Patients with exon 20 insertions had a poor response to TKIs. However, the mutation Ala763_Tyr764insPheGlnGluAla (A763_Y764 insFQEA) was related to a favorable response to TKIs. CONCLUSION: Exon 20 insertion EGFR mutations comprised a considerable group of the entire population of patients with EGFR mutations. Different first-line treatments and variants of the exon 20 insertions might be related to different outcomes in advanced NSCLCpatients.
Authors: Pedro E N S Vasconcelos; Carol Gergis; Hollis Viray; Andreas Varkaris; Masanori Fujii; Deepa Rangachari; Paul A VanderLaan; Ikei S Kobayashi; Susumu S Kobayashi; Daniel B Costa Journal: JTO Clin Res Rep Date: 2020-05-13
Authors: Keunchil Park; Eric B Haura; Natasha B Leighl; Paul Mitchell; Catherine A Shu; Nicolas Girard; Santiago Viteri; Ji-Youn Han; Sang-We Kim; Chee Khoon Lee; Joshua K Sabari; Alexander I Spira; Tsung-Ying Yang; Dong-Wan Kim; Ki Hyeong Lee; Rachel E Sanborn; José Trigo; Koichi Goto; Jong-Seok Lee; James Chih-Hsin Yang; Ramaswamy Govindan; Joshua M Bauml; Pilar Garrido; Matthew G Krebs; Karen L Reckamp; John Xie; Joshua C Curtin; Nahor Haddish-Berhane; Amy Roshak; Dawn Millington; Patricia Lorenzini; Meena Thayu; Roland E Knoblauch; Byoung Chul Cho Journal: J Clin Oncol Date: 2021-08-02 Impact factor: 50.717