- Design
- Meta-analysis of three clinical trials
- Population
- 685 patients with advanced HER2-positive gastro-oesophageal adenocarcinoma, first line
- Primary outcome
- Progression-free survival, response and adverse events
- Effect
- ORR 70% (67–74%); median PFS 12.6 months; grade 3+ treatment-related events 65%
Zanidatamab is a bispecific antibody that binds two separate sites on HER2. This meta-analysis pooled three trials with 685 patients receiving it first line with chemotherapy, with or without the PD-1 antibody tislelizumab, for advanced HER2-positive gastro-oesophageal adenocarcinoma.
The pooled response rate was 70% (95% CI 67–74%), median progression-free survival 12.6 months and reconstructed median overall survival 26.1 months. Toxicity was substantial: grade 3 or worse treatment-related events in 65%, grade 3 or worse diarrhoea in 26%, serious adverse events in 66%, left ventricular dysfunction in 6% and non-infectious lung toxicity in 4%.
Pooling single-arm and early-phase data cannot show that zanidatamab beats trastuzumab-based regimens, and overall survival was reconstructed rather than reported. The authors call for randomised data. Its regulatory status for this indication in India is not established in the candidate record.
- Expect diarrhoea in most patients on zanidatamab combinations, and severe diarrhoea in about one in four.
- Monitor left ventricular function, as with other HER2-directed therapy.
- Watch for non-infectious pneumonitis and immune-mediated effects when combined with a PD-1 antibody.
- Pooled single-arm data cannot establish superiority over trastuzumab-based first-line treatment.
Why it matters
Response rates near 70% will draw attention, and the toxicity profile needs to come with them.
Don't overread it
A meta-analysis of three mostly non-comparative trials cannot show zanidatamab is better than standard HER2 therapy.
The statistics, in plain English
A pooled median from reconstructed survival curves is an approximation. Several toxicity estimates have very wide intervals (for example, dose reduction for diarrhoea 1% to 75%) because the trials differed.
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