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.

ABSTRACT Objectives In NSCLC patients harbouring EGFR mutation, osimertinib is a third-generation tyrosine kinases inhibitor (TKI) overcoming resistance to 1st or 2nd generation EGFR- TKIs by inhibition of the EGFR exon 20 T790M mutation. However, resistance to osimertinib emerges inevitably after a few months and the resistance mechanisms remain complex and incompletely explored. We report the case of a T790M positive NSCLC patient harbouring an extremely rare molecular alteration after osimertinib resistance who responded to crizotinib. Materials and methods Next-generation sequencing (NGS) was performed on tumour, plasma and on pleural cfDNA. RESULTS In a patient who received osimertinib who showed disease progression, the MET exon 14 skipping mutation was simultaneously detected on plasma and pleural cfDNA. In consequence, the patient was administrated crizotinib and experienced durable clinical benefit, achieving an objective clinical response with this therapy. Conclusions This is the first case providing clinical evidence that crizotinib alone may be an effective therapy for overcoming resistance to osimertinib mediated by a METex14 skipping mutation. It also proves that repeating serial liquid biopsies extracted from plasma and pleural effusion, even in end-stage disease, may lead to detection of unexpected and targetable molecular findings.