Clinical response to crizotinib and emergence of resistance in lung adenocarcinoma harboring a MET c-Cbl binding site mutation. (January 2020)

• Record Type: Journal Article
• Authors: Wiesweg, Marcel; Herold, Thomas; Metzenmacher, Martin; Eberhardt, Wilfried E.; Reis, Henning; Darwiche, Kaid; Aigner, Clemens; Stuschke, Martin; Herrmann, Ken; Nensa, Felix; Schildhaus, Hans-Ulrich; Schuler, Martin
• Is Part Of: Lung cancer. Volume 139(2020)
• Page Start: 165
• Page End: 168
• Publication Date: 2020-01
• Subjects: NSCLC -- MET mutation -- Crizotinib -- c-Cbl; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2019.11.020
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Crizotinib is effective in lung cancer harboring a MET c-Cbl binding site mutation. MET c-Cbl binding site mutations constitute a distinct subtype of exon 14 mutations. Targeted therapy should be offered to patients with cancer driven by such mutations. Abstract: Objectives: MET c-Cbl binding site mutations constitute about 2 % of MET exon 14 alterations in lung cancer. Preclinical data suggests regarding these mutations as functional analogs of MET exon 14 skipping mutations, but clinical validation is lacking. Results: We report the case of a patient with metastastic lung adenocarcinoma harboring a c-Cbl binding site alteration and demonstrate clinical, radiological and metabolic response to crizotinib with a PFS of 10.6 months. As escape mechanism, a typical MET resistance mutation could be identified. Conclusion: MET c-Cbl binding site mutations should be regarded as a distinct subtype of MET exon 14 alterations. Patients with lung cancer harboring such mutations should be offered targeted therapy.