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.