‘Practice-Changing’ Data Expand Zanidatamab’s Approval to Gastroesophageal Cancer

The FDA approved zanidatamab (Ziihera) plus tislelizumab (Tevimbra) and chemotherapy as first-line treatment for unresectable/metastatic HER2-positive gastroesophageal cancer.

The approval stipulates use in adults with unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma with HER2 positivity confirmed by an FDA-approved test. The approval allows use of zanidatamab plus platinum-containing chemotherapy with or without tislelizumab. At the same time the agency approved two diagnostic tests to identify patients who are candidates for zanidatamab, a HER2-targeting bispecific antibody.

“This approval represents an important advancement in the treatment of metastatic HER2-positive GEA [gastroesophageal adenocarcinoma],” said Geoffrey Ku, MD, of Memorial Sloan Kettering Cancer Center in New York City, in a statement from Jazz Pharmaceuticals. “Importantly, similar outcomes were seen in patients whose tumors were PD-L1 positive or PD-L1 negative, suggesting that this regimen has the potential to benefit a broad range of patients.”

“It further underscores what we have known for more than 15 years: HER2 testing at the time of diagnosis for advanced or metastatic gastroesophageal adenocarcinoma is critical to optimally guide treatment selection.”

Support for the approval came from the randomized phase III HERIZON-GEA-01 trial. The primary results showed that patients who received zanidatamab plus chemotherapy, with or without the PD-1 inhibitor tislelizumab, had about a 7-month improvement in overall survival (OS; P=0.0043) and more than a 4-month improvement in progression-free survival (PFS; P<0.0001) versus trastuzumab plus chemotherapy.

Results of the trial were “truly remarkable” and “truly practice changing … and a landmark for the world of upper GI [gastrointestinal] malignancies,” said Rachna Shroff, MD, of the University of Arizona Cancer Center in Tucson, during a discussion of the study at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium. GEA is a “tough disease” that has a poor prognosis. HER2-positive disease accounts for about 20% of cases.

The most common treatment-related adverse event (AE) was diarrhea, occurring in 75% of zanidatamab-treated patients and 48% of the control group. Grade ≥3 AEs occurred in 72% of patients treated with zanidatamab and tislelizumab versus 59-60% of patients in the other two treatment groups.