Outcome of Molecular Targeted Agents Plus Chemotherapy for Second-Line Therapy of Metastatic Colorectal Cancer: A Meta-Analysis of Randomized Trials

Abstract

Introduction: The aim of this study was 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 (mCRC).

Materials and methods: We identified randomized controlled trials that compared molecular targeted agents plus chemotherapy with chemotherapy alone by searching the PubMed and Embase databases for articles published between January 2000 and September 2015. The outcome measures included progression-free survival, overall survival, objective response rate, and adverse events. Two investigators independently performed the information retrieval, screening, and data extraction. Stata 10.0 software was used to statistically analyze the extracted data. In accordance with our inclusion criteria, 11 trials, with a total of 7440 patients, were included in this meta-analysis through rounds of selection. We divided the biologic agents used into 3 subgroups based on the type of biologic agents-vascular endothelial growth factor (VEGF) inhibitor, epidermal growth factor receptor inhibitor, and other pathway inhibitors.

Results: Our results suggested that the regimen of a molecular targeted agent plus chemotherapy had a significant advantage in progression-free survival, overall survival, and objective response rate over chemotherapy alone (hazard ratio, 0.74; 95% confidence interval [CI], 0.70-0.78; hazard ratio, 0.88; 95% CI, 0.83-0.93; risk ratio, 2.24; 95% CI: 1.58-3.17, respectively). However, the rate of grade ≥ 3 adverse events was also higher in the combination therapy arm (risk ratio, 1.25; 95% CI, 1.17-1.33). Subgroup analysis showed that the combination of VEGF inhibitor with chemotherapy had a significant advantage in PFS, OS, and ORR over chemotherapy alone, but there was also a higher risk ratio in adverse events for this combination compared with the control group.

Conclusion: In conclusion, a molecular targeted agent, especially VEGF inhibitor, plus chemotherapy is a worthwhile combination for patients with metastatic colorectal cancer as second-line therapy. However, more randomized controlled trials on a larger scale are needed for evaluating the value of epidermal growth factor receptor and other pathway inhibitors.

Keywords: EGFR inhibitor; Meta-analysis; Metastatic colorectal cancer; VEGF inhibitor.