Effect of RAS status on anti-EGFR monoclonal antibodies + 5-FU infusion-based chemotherapy in first-line treatment of metastatic colorectal cancer: A meta-analysis

PURPOSE To investigate the effect of RAS on anti-EGFR moAb + 5-FU infusion based chemotherapy in first-line treatment of mCRC. METHODS The MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane databases and ClinicalTrials.gov databases were independently reviewed. Primary end points included overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicities. Correlation between RAS status and PFS, OS, ORR or toxicities was expressed as a hazard ratio (HR) or relative risk (RR). RESULTS KRAS exon 2 wild-type (-wt) mCRC benefited from adding anti-EGFR moAb (compared with chemotherapy alone: OS: HR 0.88, P = 0.008; PFS: HR 0.74, P < 0.001; ORR: RR 1.34, P = 0.003. Compared with Bevacizumab: OS: HR 0.83, P = 0.003). KRAS exon 2-wt but other RAS mutations mCRC did not benefit from adding anti-EGFR moAb. RAS-wt mCRC benefited from adding anti-EGFR moAb (compared with chemotherapy alone: OS: HR: 0.75, P < 0.001; PFS: HR 0.65, P < 0.001; ORR: RR 1.51, P = 0.020. Compared with Bevacizumab: OS: HR 0.79, P = 0.002). KRAS exon 2-wt but BRAF mutation mCRC did not benefit from adding anti-EGFR moAb. Subgroup analysis suggested that anti-EGFR moAb prolonged PFS for male, liver metastasis-only, ECOG 0-1, and colon primary site groups. Anti-EGFR moAb increased controllable grade 3-4 toxicities including rash, diarrhea, and anemia. CONCLUSIONS Adding anti-EGFR moAb as first-line treatment in RAS-wt mCRC prolonged OS. Whether BRAF mutation is a predictive marker to anti-EGFR moAb is not clear.