*6.2.2.1. Anti-EGFR monoclonal antibodies*

Cetuximab (Erbitux) is a chimeric monoclonal anti-EGFR antibody. Unfortunately, clinical trials, including the phase III EXPAND trial did not demonstrate a PFS or OS benefit for cetuximab as first-line chemotherapy in the treatment of gastric cancer [105, 106].

Panitumumab is a fully human monoclonal anti-EGFR antibody without a demonstrated efficacy in naive patients with advanced esophagogastric cancer according to the results of clinical trials including the REAL-3 study [107, 108].

Nimotuzumab is a recombinant humanized monoclonal antibody that was evaluated in a double-blind phase II trial [109] including patients with advanced gastric cancer who received nimotuzumab plus irinotecan versus irinotecan alone, showing no difference in PFS or OS between these two groups. Nevertheless, the EGFR2+/3+ subgroups presented a significant benefit when treated with nimotuzumab.

#### *6.2.2.2. TKIs of EGFR*

Gefitinib is an oral EGFR TKI currently assessed in a phase I/II study, in combination with chemoradiation, in subjects with resectable gastric cancer [110], in a phase II study in patients with unresectable and/or metastatic gastric carcinomas, and also in a phase III trial in patients with advanced gastro-esophageal junction cancers after progression on chemotherapy [111]. The results of these studies could define the role of this agent in gastric cancer treatment.

Erlotinib (Tarceva) is an oral EGFR TKI, shown to be active in a phase II trial only in patients with gastro-esophageal cancer, but not in those with gastric cancer [112].
