We report the case of a 47-year-old female patient with stage IV NSCLC harboring an echinoderm microtubule associated protein like 4 (EML4)-ALK E20;A20 fusion who was initially treated with four cycles of platinum/pemetrexed until progressive disease. Thereafter, she was treated with crizotinib for 9 months until development of evasive resistance. Subsequently, the patient was primarily resistant to alectinib and ceritinib.
We obtained low-pass copy number profiles of single isolated CTCs after the patient had experienced development of evasive resistance to crizotinib and shown primary resistance to alectinib. Furthermore, we generated additional copy number profiles of CTCs upon development of primary resistance to ceritinib. These analyses revealed the presence of an approximately eightfold MNNG HOS Transforming gene (MET) amplification in all evaluable CTCs at both time points. MET amplification (∼sevenfold) could also be detected in the cfTNA at comparable time points.
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Journal of Thoracic Oncology
DOI:10.1016/j.jtho.2018.08.2025
Authors: Lars-Arne Berger, Melanie Janning, Janna-Lisa Velthaus, Isabel Ben-Batalla, Stefanie Schatz, Markus Falk, Peter Iglauer, Ronald Simon, Ru Cao, Claudio Forcato, Nicolò Manaresi, Kelli Bramlett, Genny Buson, Annkathrin Hanssen, Markus Tiemann, Guido Sauter, Carsten Bokemeyer, Sabine Riethdorf, Martin Reck, Klaus Pantel, Harriet Wikman, and Sonja Loges