title: Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated non-small-cell lung cancer: a meta-analysis of 13 randomized trials.
abstract: Advanced non-small-cell lung cancer (NSCLC) harboring activating mutations of epidermal growth factor receptor (EGFR) are particularly sensitive to tyrosine kinase inhibitors (TKIs), namely erlotinib and gefitinib. The purpose of this meta-analysis was to evaluate the benefit of EGFR TKIs in EGFR-mutated NSCLCs. Eligible studies included published randomized controlled trials in which erlotinib or gefitinib (alone or with chemotherapy) were compared with standard therapy in 1260 patients with EGFR-mutated NSCLCs who were included in 13 trials. The mutational status was obtained through a retrospective or prospective analysis. Relative risk (RR) was calculated for response rate, and hazard ratios (HRs) were calculated for progression-free and overall survival. EGFR TKIs increase the chance of obtaining an objective response almost 2-fold when compared with chemotherapy (RR, 2.06; 2p < .00001). The response rate was 70% vs. 33.2% in first-line trials. In 3 second-line trials, response rates were 47.4% vs. 28.5%, with a benefit similar to first-line trials (RR, 1.79; 2p = .04). EGFR TKIs reduced the hazard of progression by 70% in all trials (HR, 0.30; 2p < .00001) and by 65% in first-line trials only (HR, 0.35; 2p < .00001). Overall, however, they do not improve survival (HR, 0.96; 2p = .71). NSCLCs harboring EGFR mutations derive greater benefit from erlotinib or gefitinib than from chemotherapy. All patients affected by NSCLC with an EGFR-positive mutation test result must be offered the opportunity to be treated with an EGFR TKI upfront or during the natural course of the disease if not previously exposed.
authors: Azienda Ospedaliera Treviglio-Caravaggio, Unità operativa di Oncologia, Treviglio (BG), Italy. faupe@libero.it
authors: Fausto
authors: F
authors: Petrelli
authors: Karen
authors: K
authors: Borgonovo
authors: Mary
authors: M
authors: Cabiddu
authors: Sandro
authors: S
authors: Barni
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015201:Meta-Analysis as Topic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors