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

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 EGFRTKI 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. Clinical Lung Cancer, (C) 2021 Published by Elsevier Inc.