Open Access Presentation
Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) that has been used to treat EGFR mutant lung cancers, especially those with EGFR T790M mutation. Resistance to osimertinib is likely associated with acquired genetic alterations in these cancer cells. Mesenchymal epithelial transition (MET) is a tyrosine kinase and its amplification is frequently seen in osimertinib resistant patients. To investigate whether the presence of MET alteration is associated with osimertinib resistance, a meta-analysis was conducted using published observations of EGFR mutant lung cancer patients treated with osimertinib. Frequencies of MET alterations are variable, ranging from 0-43% in osimertinib resistant patients. MET alteration is predominantly amplification, although missense mutation is seen in a few cases. Majority of the MET alterations are acquired following osimertinib treatment. Individual progression free survivals are available in two studies, and the presence of MET alteration is associated with PFS shorter than 12 months (p=0.01). These findings suggest monitoring MET alterations in osimertinib treated patient may predict resistance. With appropriate adjustment of treatment, better outcomes are likely to be achieved.
Le, Annie; Viola, Marissa; and Wang, Jun, "MET Alterations Are Associated With Osimertinib Resistance in EGFR Mutant Lung Cancers, a Meta-Analysis" (2023). Research Day. 6.