Back to Search Start Over

Genetic Heterogeneity of MET-Aberrant NSCLC and Its Impact on the Outcome of Immunotherapy

Authors :
Jan Braess
Frank Ueckeroth
Diana S.Y. Abdulla
Carina Heydt
Anna-Kristina Eisert
Frank Beckers
Wolfram Meister
Hans-Joachim Kabitz
Johann Lorenzen
Monika Serke
Sabine Merkelbach-Bruse
Sebastian Michels
Jana Fassunke
Florian Kron
A. Meyer
Gabriele Wessling
Lucia Nogova
Bernhard Schaaf
Juliane Sueptitz
Matthias Scheffler
Carsten Schaepers
Sophia Koleczko
Reinhard Buettner
Clemens Schulte
Britta Kaminsky
Richard F. Riedel
Anna Kron
Stefan Krueger
Wolfgang Schulte
Joachim Lorenz
Michael Hamm
Kato Kambartel
Anne M. Schultheis
Christian Grohé
Jürgen Wolf
Lea Ruge
Jutta Kappes
Jens Panse
Niels Reinmuth
Rieke Fischer
Source :
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 16(4)
Publication Year :
2020

Abstract

Robust data on the outcome of MET-aberrant NSCLC with nontargeted therapies are limited, especially in consideration of the heterogeneity of MET-amplified tumors (METamp).A total of 337 tumor specimens of patients with MET-altered Union for International Cancer Control stage IIIB/IV NSCLC were analyzed using next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry. The evaluation focused on the type of MET aberration, co-occurring mutations, programmed death-ligand 1 expression, and overall survival (OS).METamp tumors (n = 278) had a high frequency of co-occurring mutations (80% for all amplification levels), whereas 57.6% of the 59 patients with MET gene and exon 14 (METex14) tumors had no additional mutations. In the METamp tumors, with increasing gene copy number (GCN), the frequency of inactivating TP53 mutations increased (GCN4: 58.2%; GCN ≥ 10: 76.5%), whereas the frequency of KRAS mutations decreased (GCN4: 43.2%; GCN ≥ 10: 11.8%). A total of 10.1% of all the METamp tumors with a GCN ≥ 10 had a significant worse OS (4.0 mo; 95% CI: 1.9-6.0) compared with the tumors with GCN10 (12.0 mo; 95% confidence interval [CI]: 9.4-14.6). In the METamp NSCLC, OS with immune checkpoint inhibitor (ICI) therapy was significantly better compared with chemotherapy with 19.0 months (95% CI: 15.8-22.2) versus 8.0 months (95% CI: 5.8-10.2, p0.0001). No significant difference in median OS was found between ICI therapy and chemotherapy in the patients with METex14 (p = 0.147).METex14, METamp GCN ≥ 10, and METamp GCN10 represent the subgroups of MET-dysregulated NSCLC with distinct molecular and clinical features. The patients with METex14 do not seem to benefit from immunotherapy in contrast to the patients with METamp, which is of particular relevance for the prognostically poor METamp GCN ≥ 10 subgroup.

Details

ISSN :
15561380
Volume :
16
Issue :
4
Database :
OpenAIRE
Journal :
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Accession number :
edsair.doi.dedup.....bc23f7e85f05f773a1ed2d4bef0e7c16