Dr Shitara on Selecting First-Line Therapy in HER2+ GEA

In an interview at the 2026 ESMO Congress, Kohei Shitara, MD, director of gastrointestinal oncology at the National Cancer Center Hospital East in Kashiwa, Japan, discusses how findings from the HERIZON-GEA-01 trial (NCT05152147) may inform treatment selection for patients with HER2-positive advanced gastroesophageal adenocarcinoma (GEA).

With no head-to-head comparison between zanidatamab (Ziihera)-based therapy and trastuzumab (Herceptin) plus pembrolizumab (Keytruda) and chemotherapy, treatment decisions require consideration of the available efficacy and safety data alongside individual patient characteristics. Shitara highlights the survival benefit observed with the zanidatamab-containing triplet, including a median overall survival (OS) of 27 months and a hazard ratio of 0.65 compared with the trastuzumab-based chemotherapy control regimen. However, he also notes the increased incidence of diarrhea associated with zanidatamab-based treatment.

Shitara explains how patient fitness, comorbidities, and treatment tolerability can help guide regimen selection. For patients who are fit enough to tolerate intensive treatment, he favors the zanidatamab-containing triplet, noting that its benefit was observed regardless of PD-L1 expression. In contrast, patients who are older, frail, or have significant comorbidities may be better suited to a reduced-dose chemotherapy regimen with trastuzumab and pembrolizumab. For patients who are not candidates for immunotherapy because of coexisting autoimmune disease, zanidatamab-based chemotherapy may also be a reasonable option.

His perspective underscores the importance of individualizing first-line treatment for HER2-positive advanced GEA, balancing clinical benefit and toxicity when selecting among emerging treatment strategies.