MET Fusions in NSCLC: Clinicopathologic Features and Response to MET Inhibition.

MET fusion MET inhibition Non–small cell lung cancer Tyrosine kinase inhibitor resistance

Journal

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN: 1556-1380
Titre abrégé: J Thorac Oncol
Pays: United States
ID NLM: 101274235

Informations de publication

Date de publication:
08 Jul 2023
Historique:
received: 25 04 2023
revised: 28 06 2023
accepted: 30 06 2023
pubmed: 11 7 2023
medline: 11 7 2023
entrez: 10 7 2023
Statut: aheadofprint

Résumé

MET fusions have been described only rarely in NSCLC. Thus, data on patient characteristics and treatment response are limited. We here report histopathologic data, patient demographics, and treatment outcome including response to MET tyrosine kinase inhibitor (TKI) therapy in MET fusion-positive NSCLC. Patients with NSCLC and MET fusions were identified mostly by RNA sequencing within the routine molecular screening program of the national Network Genomic Medicine, Germany. We describe a cohort of nine patients harboring MET fusions. Among these nine patients, two patients had been reported earlier. The overall frequency was 0.29% (95% confidence interval: 0.15-0.55). The tumors were exclusively adenocarcinoma. The cohort was heterogeneous in terms of age, sex, or smoking status. We saw five different fusion partner genes (KIF5B, TRIM4, ST7, PRKAR2B, and CAPZA2) and several different breakpoints. Four patients were treated with a MET TKI leading to two partial responses, one stable disease, and one progressive disease. One patient had a BRAF V600E mutation as acquired resistance mechanism. MET fusions are very rare oncogenic driver events in NSCLC and predominantly seem in adenocarcinomas. They are heterogeneous in terms of fusion partners and breakpoints. Patients with MET fusion can benefit from MET TKI therapy.

Identifiants

DOI: 10.1016/j.jtho.2023.06.020 PMID: 37429463
pubmed: 37429463
pii: S1556-0864(23)00666-4
doi: 10.1016/j.jtho.2023.06.020
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Auteurs

Richard Riedel (R)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, Cologne, Germany.

Jana Fassunke (J)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Institute of Pathology, University of Cologne, Cologne, Germany.

Andreas H Scheel (AH)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Institute of Pathology, University of Cologne, Cologne, Germany.

Matthias Scheffler (M)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, Cologne, Germany.

Carina Heydt (C)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Institute of Pathology, University of Cologne, Cologne, Germany.

Lucia Nogova (L)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, Cologne, Germany.

Sebastian Michels (S)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, Cologne, Germany.

Rieke N Fischer (RN)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, Cologne, Germany.

Anna Eisert (A)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, Cologne, Germany.

Heather Scharpenseel (H)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, Cologne, Germany.

Felix John (F)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, Cologne, Germany.

Lea Ruge (L)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, Cologne, Germany.

Diana Schaufler (D)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, Cologne, Germany.

Janna Siemanowski (J)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Institute of Pathology, University of Cologne, Cologne, Germany.

Michaela A Ihle (MA)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Institute of Pathology, University of Cologne, Cologne, Germany.

Svenja Wagener-Ryczek (S)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Institute of Pathology, University of Cologne, Cologne, Germany.

Roberto Pappesch (R)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Institute of Pathology, University of Cologne, Cologne, Germany.

Jan Rehker (J)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Institute of Pathology, University of Cologne, Cologne, Germany.

Anne Bunck (A)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department of Radiology, University of Cologne, Cologne, Germany.

Carsten Kobe (C)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department of Nuclear Medicine, University of Cologne, Cologne, Germany.

Felix Keil (F)

Institute of Pathology, University of Regensburg, Regensburg, Germany.

Sabine Merkelbach-Bruse (S)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Institute of Pathology, University of Cologne, Cologne, Germany.

Reinhard Büttner (R)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Institute of Pathology, University of Cologne, Cologne, Germany.

Jürgen Wolf (J)

Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology, Department I of Internal Medicine, University of Cologne, Cologne, Germany; Lung Cancer Group Cologne, Cologne, Germany. Electronic address: juergen.wolf@uk-koeln.de.

Classifications MeSH