To inform about the FDA approval of zanidatamab-hrii for treating HER2-positive gastroesophageal adenocarcinoma.
Approach:
Treatment Options: Zanidatamab-hrii is approved in combination with tislelizumab-jsgr and chemotherapy for patients with HER2-positive tumors that are immunohistochemistry 3-positive or 2-positive and in situ hybridization-positive.
Clinical Trial: The approval was based on the ongoing phase 3 HERIZON-GEA-01 trial.
Key Findings:
Zanidatamab-containing regimens reduced the risk of disease progression or death by 35% compared to trastuzumab plus chemotherapy.
Median progression-free survival was 12.4 months with zanidatamab vs 8.1 months with trastuzumab.
In the overall HER2-positive population, zanidatamab plus tislelizumab and chemotherapy reduced the risk of death by 28%.
Median overall survival was 26.4 months with zanidatamab vs 19.2 months with trastuzumab.
Diarrhea was the most common adverse reaction reported.
Interpretation:
Progression-free and overall survival findings were consistent across prespecified subgroups.
Limitations:
Serious adverse reactions occurred in 59% of patients receiving zanidatamab with tislelizumab and chemotherapy.
Permanent discontinuation due to adverse reactions occurred in 13% of patients receiving zanidatamab with tislelizumab.
Conclusion:
Zanidatamab-hrii offers new first-line treatment options for patients with unresectable locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma.
The assay is indicated to identify patients with advanced melanoma who have BRAF V600E or BRAF V600K variants and may benefit from FDA-approved targeted therapies.
