title: Patients with exon 19 deletion were associated with longer progression-free survival compared to those with L858R mutation after first-line EGFR-TKIs for advanced non-small cell lung cancer: a meta-analysis.
abstract: BACKGROUND
  It has been extensively proved that the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is superior to that of cytotoxic chemotherapy in advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, the question of whether the efficacy of EGFR-TKIs differs between exon 19 deletion and exon 21 L858R mutation has not been yet statistically answered.
  
  
  METHODS
  Subgroup data on hazard ratio (HR) for progression-free survival (PFS) of correlative studies were extracted and synthesized based on random-effect model. Comparison of outcomes between specific mutations was estimated through indirect and direct methods, respectively.
  
  
  RESULTS
  A total of 13 studies of advanced NSCLC patients with either 19 or 21 exon alteration receiving first-line EGFR-TKIs were included. Based on the data from six clinical trials for indirect meta-analysis, the pooled HRTKI/chemotherapy for PFS were 0.28 (95% CI 0.20-0.38, P<0.001) in patients with 19 exon deletion and 0.47 (95% CI 0.35-0.64, P<0.001) in those with exon 21 L858R mutation. Indirect comparison revealed that the patients with exon 19 deletion had longer PFS than those with exon 21 L858R mutation (HR19 exon deletion/exon 21 L858R mutation  = 0.59, 95% CI 0.38-0.92; P = 0.019). Additionally, direct meta-analysis showed similar result (HR19 exon deletion/exon 21 L858R mutation  = 0.75, 95% CI 0.65 to 0.85; P<0.001) by incorporating another seven studies.
  
  
  CONCLUSIONS
  For advanced NSCLC patients, exon 19 deletion might be associated with longer PFS compared to L858 mutation at exon 21 after first-line EGFR-TKIs.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Kang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Fang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Zhihuang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Shaodong
authors.initials: S
authors.lastname: Hong
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Qin
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000077716:Afatinib; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D009154:Mutation; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib