Trastuzumab plus platinum–fluoropyrimidine chemotherapy has been the backbone of frontline therapy for advanced-stage HER2-positive gastroesophageal adenocarcinoma (HER2+ GEA) since 2010 on the basis of results from the landmark phase III ToGA trial. Now, data from a phase II trial indicate that zanidatamab, a biparatopic antibody targeting two distinct epitopes of HER2, might improve outcomes in this setting.

In this single-arm trial, patients with previously untreated advanced-stage HER2+ GEA received zanidatamab in combination with either 5-fluorouracil, folinic acid and oxaliplatin (n = 24), capecitabine and oxaliplatin (n = 20), or 5-fluorouracil and cisplatin (n = 2). The primary end point was confirmed objective response rate (ORR).