Precis Future Med.
2022 Dec;6(4):233-242. 10.23838/pfm.2022.00058.
Evaluation of MET alteration in EGFR-mutant non-small cell lung cancer patients treated with EGFR tyrosine kinase inhibitor from paired biopsy: A retrospective cohort study
- Affiliations
-
- 1Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- 2Sungkyunkwan University School of Medicine, Seoul, Korea
- 3Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- 4Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- KMID: 2538088
- DOI: http://doi.org/10.23838/pfm.2022.00058
Abstract
- Purpose
Mesenchymal-epithelial transition tyrosine kinase receptor (MET) amplification is one of the common acquired resistance mechanisms to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). To evaluate the usefulness of screening methods for MET status, we studied the impact of MET amplification or protein overexpression in EGFR-mutant non-small cell lung cancer patients who were treated with EGFR TKI.
Methods
A total of 214 patients treated with EGFR TKI as first-line therapy with available tissue biopsy was analyzed. Paired biopsies were obtained from 111 patients at baseline and at onset of resistance. MET status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
Results
Among 111 patients with paired samples, incidence of MET alteration was increased according to both MET overexpression by IHC (14.4% to 22.5%) and MET amplification by FISH (1.8% to 8.1%) with moderated to strong IHC intensity samples after EGFR TKI treatment. In patients treated with 1st-generation EGFR TKI, MET amplification by FISH was significantly related to shorter progression-free survival (P=0.04) and overall survival (P=0.01). In contrast, there was no difference in clinical outcomes according to MET intensity of IHC. Patients harboring MET amplification by FISH were associated with poor clinical outcomes compared to those with T790M mutation at progression.
Conclusion
These results suggest that FISH is more informative than IHC for identification of patients with MET amplification as an EGFR TKI resistance mechanism. Given the poor outcome in patients who developed MET amplification, combinational trials with more active MET inhibitor are needed to overcome resistance.
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