Revisitingmet: Clinical Characteristics And Treatment Outcomes Of Patients With Locally Advanced Or Metastatic,Met-Amplifiedesophagogastric Cancers

Background Metastatic esophagogastric cancers (EGCs) have a poor prognosis with an approximately 5% 5-year survival. Additional treatment approaches are needed. c-MET gene-amplified tumors are an uncommon but potentially targetable subset of EGC. Clinical characteristics and outcomes were evaluated in patients withMET-amplified EGC and compared with those withoutMETamplification to facilitate identification of these patients and possible treatment approaches. Patients and Methods Patients with locally advanced or metastaticMET-amplified EGC at Massachusetts General Hospital (MGH) were identified using fluorescent in situ hybridization analysis, with a gene-to-control ratio of >= 2.2 defined as positive. Non-MET-amplified patients identified during the same time period who had undergone tumor genotyping and treatment at MGH were evaluated as a comparison group. Results We identified 233 patients evaluated forMETamplification from 2002 to 2019.METamplification was seen in 28 (12%) patients versus 205 (88%) patients without amplification. MostMET-amplified tumors occurred in either the distal esophagus (n= 9; 32%) or gastroesophageal junction (n= 10; 36%). OfMET-amplified patients, 16 (57%) had aTP53mutation, 5(18%) hadHER2co-amplification, 2 (7.0%) hadEGFRco-amplification, and 1 (3.5%) hadFGFR2co-amplification.MET-amplified tumors more frequently had poorly differentiated histology (19/28, 68.0% vs. 66/205, 32%;p= .02). Progression-free survival to initial treatment was substantially shorter for allMET-amplified patients (5.6 vs. 8.8 months,p= .026) and for those with metastatic disease at presentation (4.0 vs. 7.6 months,p= .01). Overall, patients withMETamplification had shorter overall survival (19.3 vs. 24.6 months,p= .049). No difference in survival was seen between lowMET-amplified tumors (>= 2.2 and METcopy number) compared with highly amplified tumors (>= 25METcopy number). Conclusion MET-amplified EGC represents a distinct clinical entity characterized by rapid progression and short survival. Ideally, the identification of these patients will provide opportunities to participate in clinical trials in an attempt to improve outcomes. Implications for Practice This article describes 233 patients who receivedMETamplification testing and reports (a) a positivity rate of 12%, similar to the rate of HER2 positivity in this data set; (b) the clinical characteristics of poorly differentiated tumors and nodal metastases; and (c) markedly shorter progression-free survival and overall survival in MET-amplified tumors. Favorable outcomes are reported for patients treated with MET inhibitors. Given the lack of published data inMET-amplified esophagogastric cancers and the urgent clinical importance of identifying patients withMETamplification for MET-directed therapy, this large series is a valuable addition to the literature and will have an impact on future practice.