Efficacy of EGFR Tyrosine Kinase Inhibitors in Patients With EGFR-Mutated Non-Small-Cell Lung Cancer: A Meta-Analysis of 13 Randomized Trials
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- 作者：Fausto Petrelli ; faupe@libero.it ; Karen Borgonovo ; Mary Cabiddu ; Sandro Barni
- 关键词：EGFR ; Erlotinib ; Gefitinib ; Mutation ; Non&ndash ; small-cell lung cancer
- 刊名：Clinical Lung Cancer
- 出版年：2012
- 出版时间：March, 2012
- 年：2012
- 卷：13
- 期：2
- 页码：107-114
- 全文大小：472 K
文摘
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.