Durable Complete Response of Metastatic Gastric Cancer with Anti-Met Therapy Followed by Resistance at Recurrence

A 48-year-old woman with chemorefractory metastatic gastric cancer to the liver was treated in a phase I clinical trial with MetMAb, a monoclonal antibody targeting the Met tyrosine kinase receptor. The primary tumor had high MET gene polysomy and evidence for an autocrine production of hepatocyte growth factor, the growth factor ligand of Met. A complete response was obtained that lasted 2 years; the cancer recurred as a peritoneal deposit invading into the transverse colon and a gastrohepatic ligament node. Compassionate use of MetMAb therapy at recurrence achieved a mixed response: a partial response of the two initial lesions but with development of multiple new foci of carcinomatosis. Tissue and serum studies to evaluate the Met signaling pathway correlated with MetMAb treatment response initially and at the time of recurrence. SIGNIFICANCE: This research brief is the first to describe a durable complete response obtained with a molecularly targeted monoclonal antibody, MetMAb, to the receptor tyrosine kinase, Met, in a patient with chemorefractory metastatic gastric cancer. It is also the first to report biomarkers that predicted therapeutic response to Met inhibition. Cancer Discovery; 1(7); 573-9. (C) 2011 AACR.