Purpose: We performed a systematic review and meta-analysis to investigate the efficacy and toxicities of combination maintenance therapy for the treatment of advanced colorectal cancer (CRC). Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing combination maintenance therapy in advanced CRC patients were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS) and grade 3-4 toxicities. Results: A total of 3,174 advanced CRC patients received combination maintenance treatment from 6 RCTs were included for analysis. The use of combination maintenance therapy did not significantly improved PFS (HR 0.95, 95%CI: 0.75-1.20, p=0.67) and OS (HR 1.05, 95%CI: 0.93-1.17, p=0.45) in comparison with single bevacizumab maintenance therapy for the treatment of advanced CRC, similar results were observed in sub-group analysis according to treatment regimens. In addition, combination maintenance therapy significantly improved PFS (HR 0.57, 95%CI: 0.41-0.80, p=0.001), but not for OS (HR 0.93, 95%CI: 0.76-1.14, p=0.47) in comparison with observation. Additionally, more incidences of any grade 3-4 toxicities (diarrhea, fatigue and hand-foot skin reaction) were observed in the combination maintenance therapy. Conclusions: The findings of this study show that the efficacy of combination maintenance therapy is comparable to that of bevacizumab alone in terms of PFS and OS for advanced CRC patients, but at the cost of increased grade 3-4 toxicities. Thus single agent bevacizumab remains the recommended maintenance treatment for advanced CRC patients.

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