cabozantinib + osimertinib

Cabozantinib + osimertinib is a combination therapy that targets multiple resistance mechanisms in EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib is a third-generation EGFR tyrosine kinase inhibitor that targets both EGFR-sensitizing mutations and the T790M resistance mutation. Cabozantinib is a multi-target tyrosine kinase inhibitor that inhibits MET, RET, and other kinases. This combination is particularly valuable in treating patients who have developed resistance to osimertinib monotherapy through MET amplification or MET point mutations such as D1228N, D1228H, and L1195V. The combination has shown synergistic inhibition of AKT signaling and cell viability in osimertinib-resistant cancer cells.