title: Meta-analysis of EGFR tyrosine kinase inhibitors compared with chemotherapy as second-line treatment in pretreated advanced non-small cell lung cancer.
abstract: BACKGROUND
  Since efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy in the treatment of patients with pretreated advanced non-small cell lung cancer (NSCLC) remain controversial, we performed a meta-analysis to compare them.
  
  
  METHODS
  An internet search of several databases was performed, including PubMed, Embase, and the Cochrane database. Randomized trials that compared an EGFR-TKI with chemotherapy in the second-line setting were included. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade 3-4 toxicities. The PFS, OS for the EGFR mutation-positive (EGFR M+) and EGFR mutation-negative (EGFR M-) subgroups were pooled. The pooled hazard ratios (HRs) and odds ratios (ORs) with their corresponding confidence intervals (CIs) were calculated on the STATA software.
  
  
  RESULTS
  Our meta-analysis combined 3,825 patients from 10 randomized trials. Overall, EGFR-TKIs and second-line chemotherapy have equivalent efficacy in terms of PFS (HR, 1.03; 95%CI, 0.87-1.21; P = 0.73; I2 = 78.7%, Pheterogeneity<0.001), OS (HR, 1.00; 95%CI, 0.92-1.08; P = 0.90; I2 = 0.0%, Pheterogeneity = 0.88), and ORR (OR, 1.34; 95%CI, 0.86-2.08; P = 0.20; I2 = 73.1%, Pheterogeneity<0.001). However, subgroup analysis based on EGFR mutation status showed that second-line chemotherapy significantly improved PFS (HR, 1.35; 95%CI, 1.09-1.66; P = 0.01; I2 = 55.7%, Pheterogeneity = 0.046) for EGFR M- patients, whereas OS was equal (HR, 0.96; 95%CI, 0.77-1.19; P = 0.69; I2 = 0.0%, Pheterogeneity = 0.43); EGFR-TKIs significantly improved PFS (HR, 0.28; 95%CI, 0.15-0.53; P<0.001; I2 = 4.1%, Pheterogeneity = 0.35) for EGFR M+ patients, whereas OS was equal (HR, 0.86; 95%CI, 0.44-1.68; P = 0.65; I2 = 0.0%, Pheterogeneity = 0.77). Compared with chemotherapy, EGFR-TKIs led to more grade 3-4 rash, but less fatigue/asthenia disorder, leukopenia and thrombocytopenia.
  
  
  CONCLUSIONS
  Our analysis suggests that chemotherapy in the second-line setting can prolong PFS in EGFR M- patients, whereas it has no impact on OS. EGFR-TKIs seem superior over chemotherapy as second-line therapy for EGFR M+ patients. Our findings support obtaining information on EGFR mutational status before initiation of second-line treatment.
authors.affiliation: Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Breast Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ou
authors.affiliation: Department of Thoracic Surgery, Tianjin First Center Hospital, Tianjin, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Song-liang
authors.initials: SL
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Si-yu
authors.initials: SY
authors.lastname: Wang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D066246:ErbB Receptors