Outcome Of Molecular Targeted Agents Plus Chemotherapy For Second-line Therapy Of Metastatic Colorectal Cancer: A Meta-analysis Of Randomized Trials

Objectives: The aim of this study is to evaluate the efficacy and toxicity of molecular targeted agents plus chemotherapy compared with chemotherapy alone as second-line therapy for patients with metastatic colorectal cancer(m CRC).Background: Colorectal cancer(CRC) is a serious public health problem and metastatic CRC(m CRC) also poses more threats to human life. In 2015, statistics showed that colorectal cancer was one of five commonly diagnosed cancers in China. Therefore, those are great problems to prolong the patients' survival, reduce side effects and improve the quality of life. At present, the targeted agents have benefits to many patients, but their side effects also may not be ignored. Thus, we performed this meta-analysis.Methods: We identified randomized controlled trials(RCTs) meeting inclusion criteria, which compared molecular targeted agent plus chemotherapy with chemotherapy alone by using Pubmed, Embase and Ovid database, ranging from January 2000 to September 2015. The outcome measures were made up of progression-free survival(PFS), overall survival(OS), objective response rate(ORR), and adverse events. Two investigators independently performed information retrieval, screening and data extraction. Stata 10.0 software was used to statistically analyze the extracted data.Results: In accordance with inclusion criteria, eleven trials, a total of 7440 patients, were included in this meta-analysis through rounds of selection. Based on the type of molecular targeted agents, we divided these biologics into three subgroups—vascular endothelial growth factor(VEGF) inhibitor, other pathway inhibitors and epidermal growth factor receptor(EGFR) inhibitor. Our results suggested that the regimens of molecular targeted agents plus chemotherapy had a significant advantage in PFS, OS and ORR over chemotherapy alone(hazard ratio(HR) =0.74, 95% confidence interval(CI): 0.70-0.78; HR=0.88, 95% CI: 0.83-0.93; risk ratio(RR) =2.24, 95% CI: 1.58-3.17, respectively). However, the rate of adverse events(grade ? 3) was also higher in the combination therapy arm(RR=1.25, 95% CI: 1.17-1.33). Subgroup analysis showed combination VEGF inhibitor with chemotherapy had a significant advantage in PFS, OS and ORR over chemotherapy alone, but there was also a higher RR in adverse events compared with control group.Conclusions: In conclusion, molecular targeted agents plus chemotherapy have a significant advantage in PFS, OS and ORR over chemotherapy alone for m CRC patients as second-line therapy, molecular targeted drugs are effective agents, especially VEGF inhibitor.