A Case Report of Successful Treatment With Crizotinib to Overcome Resistance to Osimertinib in an EGFR Mutated Non–Small-Cell Lung Cancer Patient Harboring an Acquired MET Exon 14 Mutation

• Published in: Clinical lung cancer Vol. 23; no. 2; pp. e131 - e134
• Main Authors: Pinquie, François, Cortot, Alexis B., Chevalier, Louise-Marie, Morel, Alain, Sandrini, Jérémy, Guguen, Camille, Morvan, Benjamin, Molinier, Olivier
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2022
• Subjects: Acrylamides - therapeutic use; Aniline Compounds - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Crizotinib - therapeutic use; Drug Resistance, Neoplasm - drug effects; ErbB Receptors - metabolism; Humans; Lung Neoplasms - diet therapy; Lung Neoplasms - genetics; Male; METex14 skipping mutation; Mutation; Resistance to osimertinib; Response to crizotinib; T790M positive Non–small-cell lung cancer; Response to crizotinib; Resistance to osimertinib; T790M positive Non–small-cell lung cancer; METex14 skipping mutation
• ISSN: 1525-7304; 1938-0690; 1938-0690
• DOI: 10.1016/j.cllc.2021.06.002

•What is already known about this subject?•Resistance mechanisms to osimertinib in T790M positive NSCLC patients are multiple and heterogeneous, combining de novo EGFR alterations (C797S mutation), EGFR-independent mechanisms (MET and HER-2 amplifications) or histological transformations.•METex14 skipping alteration is an extremely rare resistance mechanism to osimertinib and can be explained either by drug selection of pre-existing minority subclones or by emergence of de novo molecular alteration.•In the rare patients who were resistant to osimertinib and who were tested for MET alteration, objective responses were reported after a combination of EGFR-TKI and crizotinib.•Liquid and tumor biopsies are rarely performed in routine practice after emergence of osimertinib resistance•What are the new findings and how might they impact on clinical practice in the foreseeable future?•We present the first case report demonstrating that crizotinib administrated alone can be effective long-term in this setting.•Repeating serial liquid biopsy, including pleural fluid, even in end-stage disease, may lead to detection of unexpected and targetable molecular findings, including MET alterations in cfDNA.