Title |
Outcome of EGFR-mutated NSCLC patients with MET-driven resistance to EGFR tyrosine kinase inhibitors
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Published in |
Oncotarget, October 2017
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DOI | 10.18632/oncotarget.21707 |
Pubmed ID | |
Authors |
Simon Baldacci, Julien Mazieres, Pascale Tomasini, Nicolas Girard, Florian Guisier, Clarisse Audigier-Valette, Isabelle Monnet, Marie Wislez, Maurice Pérol, Pascal Dô, Eric Dansin, Charlotte Leduc, Etienne Giroux Leprieur, Denis Moro-Sibilot, David Tulasne, Zoulika Kherrouche, Julien Labreuche, Alexis B. Cortot |
Abstract |
Several mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC have been described including the T790M mutation and MET amplification. Whereas T790M mutation confers prolonged survival and sensitivity to 3rd generation TKIs, data are lacking on clinical features and outcome of MET-driven resistant EGFR-mutated NSCLC patients. Patients with metastatic EGFR-mutated NSCLC displaying high MET overexpression or MET amplification, detected on a biopsy performed after progression on EGFR TKI, were identified in 15 centers. Clinical and molecular data were retrospectively collected. Forty two patients were included. The median overall survival (OS), and the median post EGFR TKI progression overall survival (PPOS) were 36.2 months [95%CI 27.3-66.5] and 18.5 months [95%CI 10.6-27.4] respectively. Nineteen out of 36 tumors tested for MET FISH had MET amplification. A T790M mutation was found in 11/41 (26.8%) patients. T790M-positive patients had a better OS than T790M-negative patients (p=0.0224). Nineteen patients received a MET TKI. Objective response was reported in 1 out of 12 evaluable patients treated with a MET inhibitor as a single agent and in 1 of 2 patients treated with a combination of MET and EGFR TKIs. MET-driven resistance to EGFR TKI defines a specific pattern of resistance characterized by low objective response rate to MET inhibitors given alone and overlapping with T790M mutations. Further studies are warranted to define adequate therapeutic strategies for MET-driven resistance to EGFR TKI. |
X Demographics
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France | 3 | 75% |
Unknown | 1 | 25% |
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Type | Count | As % |
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Members of the public | 2 | 50% |
Scientists | 1 | 25% |
Practitioners (doctors, other healthcare professionals) | 1 | 25% |
Mendeley readers
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Unknown | 19 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 4 | 21% |
Student > Bachelor | 3 | 16% |
Student > Ph. D. Student | 3 | 16% |
Other | 2 | 11% |
Professor > Associate Professor | 2 | 11% |
Other | 2 | 11% |
Unknown | 3 | 16% |
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Psychology | 1 | 5% |
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Social Sciences | 1 | 5% |
Other | 1 | 5% |
Unknown | 4 | 21% |