FDA approves new first-line options for advanced HER2-positive gastroesophageal cancer

Adults with previously untreated, advanced HER2-positive gastroesophageal cancer now have new first-line options in the United States. The FDA approved zanidatamab with fluoropyrimidine- and platinum-containing chemotherapy, either alone or alongside the immunotherapy tislelizumab. The decision covers unresectable locally advanced or metastatic adenocarcinomas of the stomach, gastroesophageal junction or esophagus, with HER2 positivity confirmed by an approved test.

Evidence came from the global, randomized HERIZON-GEA-01 trial involving 914 patients. Those receiving the three-drug regimen of zanidatamab, tislelizumab and chemotherapy had median overall survival of 26.4 months, compared with 19.2 months for trastuzumab and chemotherapy. Median progression-free survival was 12.4 months versus 8.1 months. Benefits were observed across PD-L1 subgroups, including among people whose tumors were PD-L1 negative. Zanidatamab with chemotherapy also significantly delayed disease progression, although its interim overall-survival result was not statistically significant.

The FDA also approved two companion diagnostic tests to help identify eligible patients. Treatment can carry substantial risks: grade 3 or worse adverse events occurred in 72% of patients receiving the three-drug regimen, and diarrhea was particularly common. Careful monitoring and management will therefore be important as the options enter clinical use.