Experience of treatment of a patient with non-small cell lung cancer with met exon 14 skipping

Personalized therapy is starting to play an increasing role in modern approaches to the treatment of oncological diseases. The previously existing uniform standard for each malignant disease is expanded with new options and treatment possibilities, depending on each specific clinical situation. That increases the  effectiveness of  therapy and helps to control the  disease. A  separate niche in the individual approach to anti-tumor treatment is occupied by targeted therapy of malignancies. There are a lot of mutations that can lead to the emergence of malignant neoplasms. So of all that multitude of choices the individual approach to a patient helps to select the mutations that are most likely to be found in a given patient. The research in the area of the c-MET mutation has allowed it to occupy its niche as a therapeutic target. The identification of this mutation is not included in the routine set of analyses performed for a patient with diagnosed lung adenocarcinoma. But expanding the panel of molecular testing would increase the detectability of this mutation and, as a result, improve the quality of treatment for this category of patients. This clinical case describes the experience of treatment of an elderly patient with lung adenocarcinoma, in whose tumor tissue a MET mutation was detected.

1. König D., Savic Prince S., Rothschild S.I. Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations. Cancers (Basel). 2021;13(4):804. https://doi.org/10.3390/cancers13040804.

2. Socinski M.A., Pennell N.A., Davies K.D. MET Exon 14 Skipping Mutations in Non-Small-Cell Lung Cancer: An Overview of Biology, Clinical Outcomes, and Testing Considerations. JCO Precis Oncol. 2021;5:653–663. https://doi.org/10.1200/PO.20.00516.

3. Sierra J.R., Tsao M.S. c-MET as a Potential Therapeutic Target and Biomarker in Cancer. Ther Adv Med Oncol. 2011;3(1 Suppl):S21–S35. https://doi.org/10.1177/1758834011422557.

4. Awad M.M., Oxnard G.R., Jackman D.M., Savukoski D.O, Hall D., Shivdasanietal P. et al. MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression. J Clin Oncol. 2016;34(7):721–730. https://doi.org/10.1200/JCO.2015.63.4600.

5. Titmarsh H.F., O’Connor R., Dhaliwal K., Akram A.R. The Emerging Role of the c-MET-HGF Axis in Non-small Cell Lung Cancer Tumor Immunology and Immunotherapy. Front Oncol. 2020;10:54. https://doi.org/10.3389/fonc.2020.00054.

6. Sabari J.K., Montecalvo J., Chen R., Dienstag J.A., Mrad C., Bergagnini I. et al. PD-L1 Expression and Response to Immunotherapy in Patients with MET Exon 14-Altered Non-Small Cell Lung Cancers (NSCLC). J Clin Oncol. 2017;35(15_ suppl):8512–8512. https://doi.org/10.1200/JCO.2017.35.15_suppl.8512.

7. Xing X., Guo J., Ding G., Li B., Dong B., Feng Q. et al. Analysis of PD1, PDL1, PDL2 Expression and T Cells Infiltration in 1014 Gastric Cancer Patients. Oncoimmunology. 2017;7(3):e1356144. https://doi.org/10.1080/2162402x.2017.1356144.

8. Glodde N., Bald T., van den Boorn-Konijnenberg D., Nakamura K., O’Donnell J.S., Szczepanski S. et al. Reactive Neutrophil Responses Dependent on the Receptor Tyrosine Kinase c-MET Limit Cancer Immunotherapy. Immunity. 2017;47(4):789.e9–802.e9. https://doi.org/10.1016/j.immuni.2017.09.012.

9. Papaccio F., Della Corte C.M., Viscardi G., Di Liello R., Esposito G., Sparano F. et al. HGF/MET and the Immune System: Relevance for Cancer Immunotherapy. Int J Mol Sci. 2018;19(11):3595. https://doi.org/10.3390/ijms19113595.

10. Salgia R., Sattler M., Scheele J., Stroh C., Felip E. The Promise of Selective MET Inhibitors in Non-Small Cell Lung Cancer with MET Exon 14 Skipping. Cancer Treat Rev. 2020;87:102022. https://doi.org/10.1016/j.ctrv.2020.102022.

11. Liang H., Wang M. MET Oncogene in Non-Small Cell Lung Cancer: Mechanism of MET Dysregulation and Agents Targeting the HGF/c-Met Axis. Onco Targets Ther. 2020;13:2491–2510. https://doi.org/10.2147/OTT.S231257.

12. Garajová I., Giovannetti E., Biasco G., Peters G.J. c-Met as a Target for Personalized Therapy. Transl Oncogenomics. 2015;7(Suppl 1):13–31. https://doi.org/10.4137/TOG.S30534.

13. Baltschukat S., Engstler B.S., Huang A., Hao H.X., Tam A., Wang H.Q. et al. Capmatinib (INC280) Is Active Against Models of Non-Small Cell Lung Cancer and Other Cancer Types with Defined Mechanisms of MET Activation. Clin Cancer Res. 2019;25(10):3164–3175. https://doi.org/10.1158/1078-0432.ccr-18-2814.

14. Klempner S.J., Borghei A., Hakimian B., Ali S.M., Ou S.I. Intracranial Activity of Cabozantinib in MET Exon 14-Positive NSCLC with Brain Metastases. J Thorac Oncol. 2017;12(1):152–156. https://doi.org/10.1016/j.jtho.2016.09.127.

15. Wang S.X.Y., Zhang B.M., Wakelee H.A., Koontz M.Z., Pan M., Diehn M. et al. Case Series of MET Exon 14 Skipping Mutation-Positive Non-Small-Cell Lung Cancers with Response to Crizotinib and Cabozantinib. Anticancer Drugs. 2019;30(5):537–541. https://doi.org/10.1097/CAD.0000000000000765.

16. Waqar S.N., Morgensztern D., Sehn J. MET Mutation Associated with Responsiveness to Crizotinib. J Thorac Oncol. 2015;10(5):e29–e31. https://doi.org/10.1097/JTO.0000000000000478.