Analysis of progression-free survival of first-line tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring leu858Arg or exon 19 deletions

// Feng-Che Kuan 1, 2 , Shih-Hong Li 3 , Chih-Liang Wang 3, 4 , Meng-Hung Lin 5 , Ying-Huang Tsai 6, 7 , Cheng-Ta Yang 3, 7 1 Department of Hematology and Oncology, Department of Medicine, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan 2 Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Taoyuan 33302, Taiwan 3 Department of Thoracic Medicine, Chang-Gung Memorial Hospital, Taoyuan 33305, Taiwan 4 Department of Medicine, Chang-Gung University, Taoyuan 33302, Taiwan 5 Cencer of Excellence for Chang Gung Research Datalink, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan 6 Division of Respiratory and Critical Care Medicine, Department of Medicine, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan 7 Department of Respiratory Therapy, Chang-Gung University, Taoyuan 33302, Taiwan Correspondence to: Cheng-Ta Yang, email: yang1946@cgmh.org.tw Keywords: gefitinib, erlotinib, afatinib, Leu858Arg, Thr790Met Received: August 15, 2016 Accepted: November 14, 2016 Published: December 07, 2016 ABSTRACT Background: Gefitinib, erlotinib and afatinib provide remarkable response rates and progression-free survival compared to platinum-based chemotherapy in patients with non-small cell lung cancer harboring epidermal growth factor receptor-activating mutations, and are therefore standard first-line treatment in these patients. However, no study has compared these drugs regarding progression-free survival. Materials and Methods: We conducted this retrospective study at a single medical center in Taiwan from February 16, 2011 to October 30, 2015. We used the Kaplan-Meier method to estimate survival, and multivariate Cox proportional hazard models to estimate adjusted hazard ratios and 95% confidence intervals. Findings: Of the 1006 patients diagnosed with stage IIIb and IV non-small cell lung cancer in the study period, 448 (44.5%) had EGFR-activating mutations and received first-line therapy with gefitinib ( n = 304, 67.6%), erlotinib ( n = 63, 14.3%), or afatinib ( n = 81, 18.1%). The median duration of follow-up for progression-free survival was 12.1 months in the gefitinib arm (Interquartile range [IQR]: 5.5–16.5), 11.2 months in the erlotinib arm (IQR: 4.9–16.7), and 10.3 months in the afatinib arm (IQR: 7.0–14.2). Progression-free survival was significantly longer in the patients who received afatinib or erlotinib compared to those who received gefitinib (log-rank test, p < 0.001), and the median progression-free survival was 11.4 months in the gefitinib group. Interpretation: Afatinib and erlotinib provide significant benefits in progression-free survival compared to gefitinib in first-line treatment of patients with non-small-cell lung cancers harboring EGFR-activating mutations. Further clinical trials are warranted to validate these findings.