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Genetic Heterogeneity of MET-Aberrant NSCLC and Its Impact on the Outcome of Immunotherapy
- 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.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
Lung Neoplasms
medicine.medical_treatment
MET Exon 14 Mutation
03 medical and health sciences
Exon
Genetic Heterogeneity
0302 clinical medicine
medicine
Humans
Copy-number variation
Gene
In Situ Hybridization, Fluorescence
medicine.diagnostic_test
business.industry
Genetic heterogeneity
Immunotherapy
Proto-Oncogene Proteins c-met
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Mutation
Cancer research
Immunohistochemistry
business
Fluorescence in situ hybridization
Subjects
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