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

作者：Daniel V.T. Catenacci, Les Henderson, Shu‐Yuan Xiao, Premal H. Patel, Robert L. Yauch, Priti S. Hegde, Jiping Zha, Ajay Kumar Pandita, Amy Peterson, Ravi Salgia · 发表于：Cancer Discovery · 年份：2011 · DOI：10.1158/2159-8290.cd-11-0175 · 被引用次数：112 · 研究领域：Liver physiology and pathology、Cancer Cells and Metastasis、Cholangiocarcinoma and Gallbladder Cancer Studies

UNLABELLED: A 48 year-old female with chemo-refractory metastatic gastric cancer to the liver was treated on 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 HGF, the growth factor ligand of Met. A complete response was obtained lasting two 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 evaluating the Met signaling pathway did correlate 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.