Zanidatamab in HER2-positive mGEA: quality of life and dose optimisation

In this video, Dr Filip Van Herpe discusses two analyses from the phase III HERIZON-GEA-01 trial, presented at ESMO GI 2026 in Munich.^1,2 HERIZON-GEA-01 evaluated first-line zanidatamab plus chemotherapy, with or without tislelizumab, versus trastuzumab plus chemotherapy in patients with previously untreated HER2-positive advanced or metastatic gastro-oesophageal adenocarcinoma (mGEA). The trial showed a significant improvement in progression-free survival with both zanidatamab-containing regimens, and a significant overall survival benefit with zanidatamab plus chemotherapy and tislelizumab versus trastuzumab plus chemotherapy. 

The first analysis focused on health-related quality of life.¹ Because diarrhoea is a known and frequent adverse event with zanidatamab, prophylactic loperamide was mandatory in the zanidatamab arms. Patient-reported outcomes showed that diarrhoea scores were higher early during treatment in the zanidatamab-containing arms, but this did not translate into a sustained negative impact on global health status, quality of life, or functional outcomes. After the initial treatment cycles, quality-of-life outcomes were broadly similar across treatment arms, and disease-specific symptoms were comparable. These findings suggest that the survival benefit of zanidatamab-based treatment was achieved with minimal detriment to patient-reported quality of life, provided diarrhoea is actively prevented and managed. 

The second analysis evaluated zanidatamab pharmacokinetics and dose optimisation.² Population pharmacokinetic modelling showed that body weight was the main covariate with a clinically meaningful effect on exposure, supporting the use of a two-tiered, weight-based dosing strategy. Other factors, including age, sex, race, HER2 status and mild or moderate renal or hepatic impairment, did not require dose adjustment. The analysis supported both the 1800/2400 mg every-three-weeks regimen used in HERIZON-GEA-01 and the alternative 1200/1600 mg every-two-weeks regimen, offering flexibility for combination with chemotherapy schedules.