Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr;16(4):572-582.
doi: 10.1016/j.jtho.2020.11.017. Epub 2020 Dec 9.

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

Anna Kron  1 , Matthias Scheffler  1 , Carina Heydt  2 , Lea Ruge  1 , Carsten Schaepers  1 , Anna-Kristina Eisert  1 , Sabine Merkelbach-Bruse  2 , Richard Riedel  1 , Lucia Nogova  1 , Rieke Nila Fischer  1 , Sebastian Michels  1 , Diana S Y Abdulla  1 , Sophia Koleczko  1 , Jana Fassunke  2 , Anne M Schultheis  2 , Florian Kron  3 , Frank Ueckeroth  2 , Gabriele Wessling  2 , Juliane Sueptitz  1 , Frank Beckers  4 , Jan Braess  5 , Jens Panse  6 , Christian Grohé  7 , Michael Hamm  8 , Hans-Joachim Kabitz  9 , Kato Kambartel  10 , Britta Kaminsky  11 , Stefan Krueger  12 , Clemens Schulte  13 , Joachim Lorenz  14 , Johann Lorenzen  15 , Wolfram Meister  16 , Andreas Meyer  17 , Jutta Kappes  18 , Niels Reinmuth  19 , Bernhard Schaaf  20 , Wolfgang Schulte  21 , Monika Serke  22 , Reinhard Buettner  2 , Jürgen Wolf  23
Affiliations
Free article

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

Anna Kron et al. J Thorac Oncol. 2021 Apr.
Free article

Abstract

Introduction: 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).

Methods: 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).

Results: 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 (GCN < 4: 58.2%; GCN ≥ 10: 76.5%), whereas the frequency of KRAS mutations decreased (GCN < 4: 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 GCN < 10 (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, p < 0.0001). No significant difference in median OS was found between ICI therapy and chemotherapy in the patients with METex14 (p = 0.147).

Conclusions: METex14, METamp GCN ≥ 10, and METamp GCN < 10 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.

Keywords: Immune checkpoint inhibitor therapy; MET amplification; MET exon 14 mutation; Non–small cell lung cancer.

PubMed Disclaimer

Comment in

Substances