High MET amplification level as a resistance mechanism to osimertinib (AZD9291) in a patient that symptomatically responded to crizotinib treatment post-osimertinib progression.

Third-generation EGFR TKI has been approved in the US and EU for the treatment of EGFR mutant T790M+ NSCLC patients that are resistant to first- or second generation EGFR TKIs. Here we report a patient who developed resistance to osimertinib after a confirmed partial response for 9 months. Pre-osimertinib and post-osimertinib tumor biopsy revealed the emergence of high level of MET amplification (30 copies) post osimertinib treatment. Patient was treated with single agent crizotinib, a known MET inhibitor, with transient symptomatic benefit. MET amplification is one potential resistance mechanism to osimertinib and combination of osimertinib and a MET inhibitor should be investigated post-osimertinib progression in EGFR mutant T790M+ NSCLC patients whose harbored acquired MET amplification.