Comparison of the effects of the three major tyrosine kinase inhibitors as first-line therapy for non-small-cell lung cancer harboring epidermal growth factor receptor mutations

// Chih-Yen Tu 1, 2, 3, * , Chuan-Mu Chen 1, * , Wei-Chih Liao 2, 5, 6 , Biing-Ru Wu 2 , Chih-Yu Chen 2, 6 , Wei-Chun Chen 2, 6 , Te-Chun Hsia 2, 4, 5 , Wen-Chien Cheng 2 and Chia-Hung Chen 2, 4, 5, 7 1 Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan 2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan 3 School of Medicine, China Medical University, Taichung, Taiwan 4 Department of Respiratory Therapy, China Medical University, Taichung, Taiwan 5 Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan 6 Department of Internal Medicine, Hyperbaric Oxygen Therapy Center, China Medical University, Taichung, Taiwan 7 Taiwan Clinical Trial Consortium for Lung Diseases (TCoC), Taichung, Taiwan * These authors contributed equally to this work Correspondence to: Wei-Chih Liao, email: weichih.liao@gmail.com Chia-Hung Chen, email: hsnu758@gmail.com Keywords: EGFR-mutated lung adenocarcinoma; gefitinib; erlotinib; afatinib; progression-free survival Received: August 21, 2017 Accepted: January 25, 2018 Epub: February 04, 2018 Published: May 11, 2018 ABSTRACT Introduction: Patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR)-activating mutations have good response rate and longer progression-free survival (PFS) when treated with the tyrosine kinase inhibitors (TKI) compared with platinum-based chemotherapy. However, studies comparing the effectiveness of these drugs as first-line therapy in such patients are limited. Results: We analyzed 422 patients with EGFR-mutated advanced lung adenocarcinoma receiving first-line gefitinib ( n = 195, 46.2%), erlotinib ( n = 123, 29.1%), or afatinib ( n = 104, 24.6%). The PFS of the afatinib group was longer (12.2 months) than that of the gefitinib group (9.8 months) ( p = 0.035) but similar to that of the erlotinib group (11.4 months) ( p = 0.38). In patients without brain metastasis (BM), subgroup analysis showed that the afatinib group had significantly longer PFS (13.1 months) than erlotinib (11.7 months) and gefitinib (9.8 months) groups ( p = 0.010). Patients with exon 19 deletions in the afatinib and erlotinib groups had potentially long PFS ( p = 0.073). Efficacy of afatinib was similar between the 30 mg and 40 mg arms (median PFS 16.1 months vs. 10.3 months; p = 0.923). Conclusions: Afatinib may be the optimal EGFR-TKI for advanced lung adenocarcinoma harboring EGFR-activating mutations, particularly in the absence of BM. Patients with exon 19 deletions taking afatinib had potentially long PFS. An afatinib dose of 30 and 40 mg has similar effect. Methods: We conducted this retrospective study at a single medical center from January 2013 to March 2017 and used PFS to evaluate the effectiveness of gefitinib, erlotinib, and afatinib in patients with advanced lung adenocarcinoma harboring EGFR mutations.