Purpose: This study compared the efficacy and toxicities of cetuximab combined with chemotherapy versus chemotherapy for patients with metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on the outcomes was also investigated.
Methods: Literature retrieval, trials selection and assessment, data collection, and statistical analysis were performed according to the Cochrane Handbook 5.0.2. The outcome measures were tumor response rate, progression-free survival, overall survival, and adverse effects.
Results: Four randomized controlled trials, comprising totally 2,912 patients, were included. Meta-analysis showed higher response rate (RR 1.93; 95% CI, 1.14-3.26) and significant improvement in progression-free survival (PFS; HR 0.80; 95% CI, 0.67-0.95) in cetuximab-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding overall survival (OS; HR 0.95; 95% CI, 0.87-1.05). In wild-type KRAS patients, treatment with cetuximab plus chemotherapy significantly increased response rate (RR 1.44; 95% CI, 1.20-1.73) and improved PFS (HR 0.64; 95% CI, 0.50-0.84), as compared with chemotherapy groups, but not for OS (HR 0.84; 95% CI, 0.64-1.11). In mutant KRAS patients, there was no significant difference between those treated with cetuximab plus chemotherapy and those with chemotherapy alone regarding response rate (RR 0.81; 95% CI, 0.61-1.08), PFS (HR 1.37; 95% CI, 0.81-2.31), and OS (HR 1.03; 95% CI, 0.74-1.44). The risk of grade 3/4 rash, diarrhea, neutropenia, and fatigue was significantly increased in cetuximab combination groups as compared with chemotherapy groups.
Conclusions: The use of cetuximab in addition to chemotherapy was a valid alternative for patients with mCRC. Benefit of cetuximab was only limited to patients with wild-type KRAS tumors.