Adults with unresectable locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma now have 2 first-line treatment options containing zanidatamab-hrii (Ziihera) following approval by the US Food and Drug Administration, according to a press release from Jazz Pharmaceuticals.
Zanidatamab-hrii plus tislelizumab-jsgr and fluoropyrimidine- and platinum-containing chemotherapy is indicated in patients with HER2-positive tumors that are immunohistochemistry 3-positive or immunohistochemistry 2-positive and in situ hybridization-positive. Zanidatamab-hrii plus fluoropyrimidine- and platinum-containing chemotherapy is indicated in patients with HER2-positive tumors that are immunohistochemistry 3-positive.
The approval was based on results from the ongoing phase 3 HERIZON-GEA-01 trial. Both zanidatamab-containing regimens reduced the risk of disease progression or death by 35% vs trastuzumab plus chemotherapy. Median progression-free survival was 12.4 months with the zanidatamab-containing regimens vs 8.1 months with trastuzumab plus chemotherapy.
In the overall HER2-positive population, zanidatamab-hrii plus tislelizumab-jsgr and chemotherapy reduced the risk of death by 28% vs trastuzumab plus chemotherapy. Median overall survival was 26.4 months vs 19.2 months, respectively. Progression-free and overall survival findings were similar across prespecified subgroups, including those defined by geographic region and programmed death ligand 1 status.
Diarrhea was the most common adverse reaction reported with the zanidatamab-containing regimens. The prescribing information includes boxed warnings for diarrhea and embryo-fetal toxicity. Serious adverse reactions occurred in 59% of patients who received zanidatamab-hrii with tislelizumab-jsgr and chemotherapy and 49% of those who received zanidatamab-hrii with chemotherapy. Permanent discontinuation of zanidatamab-hrii because of adverse reactions occurred in 13% and 10% of patients, respectively.
Zanidatamab-hrii is a bispecific antibody designed to target 2 extracellular HER2 binding sites. Gastroesophageal adenocarcinoma includes cancers of the stomach, gastroesophageal junction, and esophagus, and approximately 20% of patients have HER2-positive disease.
Source: Jazz Pharmaceuticals
