Is There Merit for MET-Targeted Therapies in Gastroesophageal Cancer?

To the Editor A recent study published in JAMA Oncology evaluated the effect of the MET inhibitor onartuzumab in combination with standard first-line chemotherapy in patients with advanced human epidermal growth factor receptor 2–negative, mesenchymal-epithelial transition (MET)–positive gastroesophageal carcinoma. MET positivity was defined as at least 50% of cells staining positive with intensity of 1+ or greater. This randomized phase 3 trial was stopped early because no improvement in progression-free survival, overall survival, or overall response rate was seen in the arm treated with chemotherapy and onartuzumab, irrespective of MET expression status. These negative results are in line with previously published phase 2/3 trials showing disappointing results with MET-inhibiting drugs. In their Discussion, Shah et al describe several hypotheses to explain the failure of MET inhibitors, more specifically MET overexpression not being the appropriate target or MET signaling being a consequence rather than the cause of tumor growth, concluding that better predictive biomarkers are needed.

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