The role of anti-EGFR agents in the first-line treatment of advanced esophago-gastric adenocarcinoma: a meta-analysis

The role of anti-epidermal growth factor receptor (EGFR) therapy is controversial in patients with esophago-gastric adenocarcinoma. We performed this meta-analysis to evaluate whether the addition of an anti-EGFR agent to chemotherapy can produce survival benefits in patients with advanced esophageal adenocarcinoma, gastric adenocarcinoma, or gastroesophageal junction adenocarcinoma. Electronic databases were searched for eligible randomized studies. From six studies, 1,817 patients were included in the meta-analysis of hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS). Compared with chemotherapy alone, anti-EGFR agents in combination with chemotherapy were significantly associated with shorter PFS (HR = 1.14 [95% confidence interval {CI}, 1.01-1.28], P = 0.03). In terms of OS, the addition of an anti-EGFR agent to chemotherapy showed no advantage (HR = 1.10 [95% CI, 0.98-1.23], P = 0.11). In addition, the combination of an anti-EGFR agent with chemotherapy significantly increased some grade 3/4 toxicities including diarrhea (risk ratio {RR} = 1.42, [95% CI, 1.03-1.94], P = 0.03), mucositis (RR = 3.30 [95% CI, 1.54-7.07], P = 0.002), and skin rash (RR = 6.82 [95% CI, 3.15-14.78], P < 0.00001). In conclusion, this meta-analysis indicates that the addition of an antiEGFR agent to chemotherapy conveys no additional benefit for patients with advanced esophago-gastric adenocarcinoma. As of now, anti-EGFR agents should not be used in the first-line treatment of adenocarcinoma of the upper gastrointestinal tract.