FCGR2A and FCGR3A polymorphisms predict prognosis in metastatic colorectal cancer patients treated with cetuximab-based therapies: a systematic review and meta-analysis

A meta-analysis of the FCGR2A H131R and FCGR3A V158F polymorphisms in patients with metastatic colorectal cancer was performed to assess the association between these genetic polymorphisms and the clinical efficacy and prognostic value of cetuximab-based therapies. A search of the PubMed and EMBASE databases identified 11 published studies including 907 patients treated with cetuximab-based regimens. The clinical response, disease control rate (DCR), and prognosis were evaluated using a fixed or random effects model. Patients carrying the FCGR2A 131R allele (HR and RR genotypes) had a better clinical response than those with the FCGR2A 131HH genotype in the overall pooled analysis (HR+RR vs. HH; overall response rate (ORR) = 1.54; 95% confidence interval (CI) = 1.31-2.09; P = 0.01) and in subgroup analysis of patients who received cetuximab as a single agent (HR+RR vs. HH; ORR = 1.77; 95% CI = 0.95-3.28; P = 0.07). No significant association between the FCGR2A 131H/R polymorphism and DCR or prognostic factors was observed. Patients harboring the FCGR3A 158F allele had better DCR than those with the FCGR3 158VV genotype (VF+FF vs. VV; DCR = 1.45; 95% CI = 1.04-2.05; P = 0.03), whereas no significant differences between the two groups were observed in the clinical response rate or prognostic factors. Pooled analysis showed that FCGR3A V allele carriers had a better clinical response (VV+VF vs. FF; ORR = 0.59; 95% CI = 0.35-0.99; P = 0.05) and longer overall survival than those with the FCGR3A FF genotype (VV+VF vs. FF; HR = 0.79; 95% CI = 0.64-0.97; P = 0.03). This meta-analysis showed that the FCGR polymorphism is associated with treatment efficacy and the prognosis of patients with metastatic colorectal cancer treated with cetuximab.