Smyth EC, et al. - Via a randomized phase 2 study on 441 patients with resectable gastroesophageal cancer researchers determined the safety of adding lapatinib to epirubicin, cisplatin, and capecitabine (ECX) chemotherapy and to find a suggested dose regimen for a phase 3 trial. No dose increase was done in two of the first 10 patients in the modified ECX plus lapatinib arm as preoperative grade 3 diarrhea was reported. With some increase in toxic effects, 1,250 mg of lapatinib administration per day in combination with ECX chemotherapy was reasonable, without the compromise of operative management, but toxic effects exceeded predefined acceptable parameters. Similar postoperative complication rates in each arm were found. A translational protocol, which would involve genomic, transcriptomic, and proteomic analysis of Human Epidermal Growth Factor Receptor 2-associated signaling pathways is planned. To further clarify possibilities for targeting HER2 in this challenging heterogenous disease, it is expected that these results would be a helping hand.