Combination of Crizotinib and Osimertinib in T790M+ EGFR-Mutant Non-Small Cell Lung Cancer with Emerging MET Amplification Post-Osimertinib Progression in a 10-Year Survivor: A Case Report

Abstract

Tyrosine kinase inhibitors (TKIs) represent the standard treatment for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The duration of the response is, however, limited in time owing to the development of resistance mechanisms to both first- and second-generation agents such as MET oncogene amplification. This report describes the successful results obtained with the combination of the third-generation TKI osimertinib with the multitargeted TKI and MET inhibitor crizotinib in a patient with EGFR-mutant NSCLC with emerging MET amplification with a tolerable toxicity profile.

Keywords: EGFR mutation; MET amplification; Non-small cell lung cancer; Targeted therapy.

Fig. 1

Results of the molecular pathological analysis. Upper panels: IGV (Integrative Genomics Viewer) displays of the detected EGFR mutations (referred to refseq ID NM_005228); left: exon 19 deletion EGFR:p.E746_A750delELREA with a frequency of 68%; right: point mutation EGFR:p.T790M with a frequency of 29%. Lower panels: detection of the MET amplification; left: CNV analysis based on the coverage of the next-generation sequencing data; right: representative image of chromogenic in situ hybridization with a nucleic signal for the centromeric region of chromosome 7 (CEP7; red) and the MET gene locus (green). An evaluation of more than 20 tumor cells in two distinct regions of the tumor showed a clear increase in MET signals with a clustered pattern and a MET/CEP7 ratio of 6.9.

Fig. 2

Schematic summary of the combined treatment and the clinical course.