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Outcome of EGFR-mutated NSCLC patients with MET-driven resistance to EGFR tyrosine kinase inhibitors
- Source :
- Oncotarget, Oncotarget, Impact journals, 2017, 8 (62), pp.105103-105114. ⟨10.18632/oncotarget.21707⟩, Oncotarget, 2017, 8 (62), pp.105103-105114. ⟨10.18632/oncotarget.21707⟩
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
Abstract
- // Simon Baldacci 1, 15 , Julien Mazieres 2 , Pascale Tomasini 3 , Nicolas Girard 4 , Florian Guisier 5 , Clarisse Audigier-Valette 6 , Isabelle Monnet 7 , Marie Wislez 8 , Maurice Perol 9 , Pascal Do 10 , Eric Dansin 11 , Charlotte Leduc 12 , Etienne Giroux Leprieur 13 , Denis Moro-Sibilot 14 , David Tulasne 15 , Zoulika Kherrouche 1, 15 , Julien Labreuche 16 and Alexis B. Cortot 1, 15 1 CHU Lille, Thoracic Oncology Department, Univ. Lille, Siric ONCOLille, Lille, France 2 Toulouse University Hospital, Universite Paul Sabatier, Toulouse, France 3 Aix-Marseille University, Assistance Publique Hopitaux de Marseille, Multidisciplinary Oncology & Therapeutic Innovations Department, Marseille, France 4 Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, France 5 Rouen University Hospital, Thoracic oncology unit & Normandy University, IRIB, LITIS Lab, EA 4103 QuantIF team, Rouen, France 6 Service de Pneumologie, Centre Hospitalier Sainte Musse, Toulon, France 7 Centre Hospitalier Intercommunal de Creteil, Creteil, France 8 APHP Hopital Tenon, Paris, France 9 Department of Medical Oncology, Centre Leon Berard, Lyon, France 10 Centre Regional de Lutte Contre le Cancer Francois Baclesse, Caen, France 11 Centre Oscar Lambret, Lille, France 12 CHU Strasbourg, Strasbourg, France 13 APHP – Hopital Ambroise Pare, Boulogne-Billancourt, France 14 Unite d’Oncologie Thoracique, Service de Pneumologie, CHU Grenoble-Alpes, La Tronche, France 15 Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161, M3T, Mechanisms of Tumorigenesis and Targeted Therapies, Lille, France 16 EA 2694 University of Lille, Lille, France Correspondence to: Alexis B. Cortot, email: alexis.cortot@chru-lille.fr Keywords: non small cell lung cancer; EGFR; tyrosine kinase inhibitors; resistance; MET Received: February 21, 2017 Accepted: August 04, 2017 Published: October 09, 2017 ABSTRACT Background: 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. Methods: 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. Results: 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. Conclusion: 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.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
EGFR
Met amplification
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
resistance
03 medical and health sciences
T790M
0302 clinical medicine
[SDV.CAN] Life Sciences [q-bio]/Cancer
tyrosine kinase inhibitors
MET
non small cell lung cancer
Internal medicine
Thoracic Oncology
medicine
Lung cancer
Objective response
business.industry
Cancer
University hospital
medicine.disease
EGFR Tyrosine Kinase Inhibitors
3. Good health
respiratory tract diseases
030104 developmental biology
030220 oncology & carcinogenesis
[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
business
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Database :
- OpenAIRE
- Journal :
- Oncotarget, Oncotarget, Impact journals, 2017, 8 (62), pp.105103-105114. ⟨10.18632/oncotarget.21707⟩, Oncotarget, 2017, 8 (62), pp.105103-105114. ⟨10.18632/oncotarget.21707⟩
- Accession number :
- edsair.doi.dedup.....9563e0059a3acabc3c9161b495a00587