Does the Addition of Biologic Agents to Chemotherapy in Patients with Unresectable Colorectal Cancer Metastases Result in a Higher Proportion of Patients Undergoing Resection? A Systematic Review and Meta-analysis

BACKGROUND: Surgical resection provides the best opportunity for cure for metastatic colorectal cancer. Whether addition of a biologic agent to chemotherapy improves the rate of conversion from unresectable to resectable disease remains uncertain. We carried out a systematic review of the literature and meta-analysis to define the impact of biologic agents on resection. METHODS: We searched Medline, Embase, CENTRAL, and PubMed for randomized controlled trials published up until April 2017 comparing chemotherapy and biologics (intervention) vs. chemotherapy alone (control) in treatment-naïve patients with unresectable metastatic colorectal cancer. Study selection, data abstraction, risk of bias, and quality of evidence assessment were performed in duplicate. Random-effects meta-analysis was used to estimate the pooled odds ratio (OR) for resection rate and corresponding confidence interval (CI). RESULTS: Nine studies, including a total of 4345 patients, were analyzed. Seven studies assessed epithelial growth factor receptor (EGFR)-directed monoclonal antibodies, and two used antiangiogenic agents. The addition of a biologic agent to chemotherapy was associated with higher resection rate (OR 1.47, 95% CI 1.07-2.02; resection rate 8.4 vs. 6.1%). Subgroup analysis based on mechanism of action of drugs showed benefit for resection rate only with EGFR-directed agents (OR 1.70, 95% CI 1.10-2.64). Heterogeneity among studies was low (I ²  = 34%). CONCLUSIONS: The addition of biologic agents to systemic chemotherapy in patients with initially unresectable metastatic colorectal cancer improved resection rate. The optimal biologic agent for this outcome cannot yet be determined.