title: Comparison of gefitinib, erlotinib and afatinib in non-small cell lung cancer: A meta-analysis.
abstract: Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for treating advanced non-small cell lung cancer (NSCLC) with proven efficacy. We undertook a systematic review and meta-analysis to synthesize existing studies with direct comparisons of EGFR TKIs in NSCLC in terms of both efficacy and safety. Eight randomized trials and 82 cohort studies with a total of 17,621 patients were included for analysis. Gefitinib and erlotinib demonstrated comparable effects on progression-free survival (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.95 to 1.04), overall survival (HR, 0.99; 95% CI, 0.93 to 1.06), overall response rate (risk ratio [RR], 1.05; 95% CI, 1.00 to 1.11), and disease control rate (RR, 0.98; 95% CI, 0.96 to 1.01), which did not vary considerably with EGFR mutation status, ethnicity, line of treatment, and baseline brain metastasis status. Gefitinib was associated with more grade 3/4 liver dysfunction, but tended to cause lower rates of dose reduction, treatment discontinuation, total grade 3/4 adverse events (RR, 0.78; 95% CI 0.65 to 0.94), and a number of specific adverse events such as rash and diarrhea. No solid evidence was found that afatinib had greater efficacy than gefitinib or erlotinib in first-line treatment of EGFR-mutant NSCLC. However, afatinib was more effective than erlotinib as second-line treatment of patients with advanced squamous cell carcinoma. The grade 3/4 adverse events rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib.
authors.affiliation: Division of Epidemiology, the Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong, China.|The Hong Kong Branch of the Chinese Cochrane Centre, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Zuyao
authors.identifier: 0000-0003-2386-2431
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Cancer Research UK and University College London Cancer Trials Centre, 90 Tottenham Court Rd, London, W1T 4TJ, United Kingdom.
authors.forename: Allan
authors.initials: A
authors.lastname: Hackshaw
authors.affiliation: Division of Epidemiology, the Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Division of Epidemiology, the Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Fu
authors.affiliation: Division of Epidemiology, the Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Yuelun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Epidemiology, the Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong, China.|Shenzhen Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of the Chinese University of Hong Kong, Shenzhen, Guangdong Province, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Mao
authors.affiliation: Division of Epidemiology, the Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong, China.|The Hong Kong Branch of the Chinese Cochrane Centre, the Chinese University of Hong Kong, Hong Kong, China.|Shenzhen Key Laboratory for Health Risk Analysis, Shenzhen Research Institute of the Chinese University of Hong Kong, Shenzhen, Guangdong Province, China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Tang
mesh_terms: D000077716:Afatinib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D005076:Exanthema / Q000139:chemically induced; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: afatinib; erlotinib; gefitinib; meta-analysis; non-small cell lung cancer