RevisitingMET: Clinical Characteristics and Treatment Outcomes of Patients with Locally Advanced or Metastatic,MET-Amplified Esophagogastric Cancers
| العنوان: | RevisitingMET: Clinical Characteristics and Treatment Outcomes of Patients with Locally Advanced or Metastatic,MET-Amplified Esophagogastric Cancers |
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| المؤلفون: | Jill N. Allen, Surendra Pal Chaudhary, John T. Mullen, Christopher G. Azzoli, Samuel J. Klempner, Eunice L. Kwak, Jeffrey W. Clark, Theodore S. Hong, Ryan B. Corcoran, Lawrence S. Blaszkowsky, Eric Roeland, Aparna Raj Parikh, Jason E. Faris, Andrea L. Russo, Jochen K. Lennerz, Lipika Goyal, Janet E. Murphy, Rebecca S. Heist, Katie L. Hwang, A. John Iafrate, Darrell R. Borger, David P. Ryan |
| المصدر: | Oncologist |
| بيانات النشر: | Oxford University Press (OUP), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Esophageal Neoplasms, medicine.medical_treatment, Treatment outcome, Locally advanced, Met amplification, Disease, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Internal medicine, Gastrointestinal Cancer, medicine, Humans, Genotyping, In Situ Hybridization, Fluorescence, Aged, business.industry, Gene Amplification, Histology, Middle Aged, Proto-Oncogene Proteins c-met, Prognosis, Clinical trial, Treatment Outcome, 030104 developmental biology, Massachusetts, 030220 oncology & carcinogenesis, Female, Esophagogastric Junction, business |
| الوصف: | BackgroundMetastatic 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 with MET-amplified EGC and compared with those without MET amplification to facilitate identification of these patients and possible treatment approaches.Patients and MethodsPatients with locally advanced or metastatic MET-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.ResultsWe identified 233 patients evaluated for MET amplification from 2002 to 2019. MET amplification was seen in 28 (12%) patients versus 205 (88%) patients without amplification. Most MET-amplified tumors occurred in either the distal esophagus (n = 9; 32%) or gastroesophageal junction (n = 10; 36%). Of MET-amplified patients, 16 (57%) had a TP53 mutation, 5(18%) had HER2 co-amplification, 2 (7.0%) had EGFR co-amplification, and 1 (3.5%) had FGFR2 co-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 all MET-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 with MET amplification had shorter overall survival (19.3 vs. 24.6 months, p = .049). No difference in survival was seen between low MET-amplified tumors (≥2.2 and ConclusionMET-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 PracticeThis article describes 233 patients who received MET amplification 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 in MET-amplified esophagogastric cancers and the urgent clinical importance of identifying patients with MET amplification for MET-directed therapy, this large series is a valuable addition to the literature and will have an impact on future practice. |
| تدمد: | 1549-490X 1083-7159 |
| DOI: | 10.1634/theoncologist.2020-0274 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa1dee14a10324f97eabfb05e24b6979 https://doi.org/10.1634/theoncologist.2020-0274 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fa1dee14a10324f97eabfb05e24b6979 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1549490X 10837159 |
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| DOI: | 10.1634/theoncologist.2020-0274 |