Identification of a High-Level MET Amplification in CTCs and cfTNA of an ALK-Positive NSCLC Patient Developing Evasive Resistance to Crizotinib

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.
This study ..... READ ARTICLE

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

Case Study, group2Kirk SmithNovember 29, 2021Crizotinib, Resistance, MET amplification

Real-world insights into patients with advanced NSCLC and MET alterations

Heterogeneous treatments reflect the changing landscape and availability of new treatments, as well as the high unmet medical need in older, METex14 patients who had more advanced disease at diagnosis. MET-targeted therapies could be beneficial in patients with these rare MET alterations. RE AD ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.06.015

Authors: Marisa Bittonia James Chih-Hsin Yang, Jin-Yuan Shih, Nir Peled, Egbert F. Smite, D. Ross Camidge, Rajeswara Rao Arasada, Dina Okseng, Emmanuelle Boutmy, Christopher Stroh, Andreas Johne, David P. Carbonea and Paul K. Paik

Early Alectinib Resistance From MET Amplification in ALK-Rearranged NSCLC: Response to Crizotinib with Re-Response to Alectinib and Crizotinib

Crizotinib is active as second-line therapy against MET-mediated resistance to alectinib in anaplastic lymphoma kinase (ALK)-rearranged non–small-cell lung cancer and can be used in combination.

Repeat molecular analyses including assessment of MET amplification can help guide therapy in ALK-positive non–small-cell lung cancer. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2021.04.008

Authors: Jingran Ji, Anupam Mitra, D. Ross Camidge, Jonathan W. Riess

Circulating tumor cells as a response biomarker in alk-positive metastatic inflammatory myofibroblastic tumor

Case report of a 19-year-old boy with an ALK-positive IMT of the bladder, proximal osteolytic and multiple bilateral lung lesions, who received ALK inhibitor entrectinib postoperatively and underwent longitudinal CTC analysis during treatment. Antitumor activity of entrectinib was demonstrated and was accompanied by regression of lung lesions, elimination of CTCs from the blood and no development of relapses afterwards. Therapy continued without any clinical sign of progression and 24 months since the initiation of treatment the patient remains symptom-free and disease-free. READ ARTICLE

Frontiers in Pediatrics DOI:10.3389/fped.2021.652583

Authors: Paolo Bonvini, Elisabetta Rossi, Angelica Zin, Mariangela Manicone, Riccardo Vidotto, Antonella Facchinetti, Lucia Tombolan, Maria C. Affinita, Luisa Santoro, Zamarchi Rita, Gianni Bisogno.

Complex genetic alterations contribute to rapid disease progression in an ALK rearrangement lung adenocarcinoma patient: a case report

Concurrent genetic alterations, including loss-of-function mutations in FBXW7 and MLL3, may mainly contribute to poor prognosis in the patient. It highlighted the molecular profiling by using NGS can be useful in identifying the heterogeneity across lesions and the resistance mechanism of targeted treatments. READ ARTICLE

Translational Cancer Research DOI:10.21037/tcr-20-3473

Authors: Xiang Long, Hao Wu, Chenglin Yang, Fang Li, Min Zhang, Xuan Wu