Pemetrexed versus Gefitinib as Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Meta-analysis Based on Randomized Controlled Trials

Abstract Objective To investigate the clinical efficacy and toxicity of Pemetrexed versus Gefitinib as second-line treatment for advanced non-small cell lung cancer (NSCLC). Methods By systematically searching the electronic databases of Pubmed, CENTRAL, Cochrane, EMBASE, ASCO, and CBM, open published randomized clinical trials (RCTs) relevant to clinical efficacy and toxicity of Pemetrexed versus Gefitinib as second-line treatment of advanced NSCLC were included in the meta-analysis. Data of objective response rate (ORR) and drug related toxicity were extracted from the original publications and pooled by random or fixed effect method. Results Fourteen clinical trials related to Pemetrexed versus Gefitinib as second-line treatment for advanced NSCLC fulfilled the inclusion criteria and were included in the meta-analysis. The pooled results show that the ORR (RR=0.81, 95% CI:0.56–1.16, p=0.25) and DCR (RR=1.11, 95% CI:0.94–1.31, p=0.24) were not statistical different for Pemetrexed versus Gefitinib as second-line treatment of advanced NSCLC. However, the pooled data demonstrated the risk of developing skin rash (RR=0.10, 95% CI:0.03–0.30, p=0.00) and diarrhea (RR=0.31, 95% CI:0.15–0.67, p=0.003) in patients with Pemetrexed was significantly lower than that of Gefitinib through random effect model analysis, but the incidence of neutropenia in Pemetrexed group was significantly higher than that of Gefitinib with statistical difference (RR=7.62, 95% CI:3.71–15.66, p=0.00). Conclusion Pemetrexed was not inferior as second-line treatment for advanced NSCLC compared to Gefitinib for tumor response. However, Pemetrexed had higher incidence of neutropenia but lower risk of developing skin rash and diarrhea.