crizotinib + osimertinib

Crizotinib + osimertinib is a combination of two small molecule tyrosine kinase inhibitors used off-label in the treatment of advanced non-small cell lung cancer (NSCLC) with acquired resistance to EGFR-targeted therapy, particularly in cases where MET amplification emerges as a resistance mechanism. Crizotinib is a multitargeted TKI that inhibits MET, ALK, and ROS1 kinases, while osimertinib is a third-generation EGFR TKI that selectively targets both sensitizing EGFR mutations and the T790M resistance mutation. The rationale for combining these agents is to overcome dual oncogenic drivers—EGFR mutation and MET amplification—that can co-exist after progression on prior EGFR inhibitor therapy. This combination has shown clinical benefit in case reports and retrospective studies by inducing tumor regression or symptomatic improvement in patients with advanced NSCLC harboring both EGFR mutations (including T790M) and acquired MET amplification[1][2][3][4].

Brand names

Xalkori (for crizotinib)Tagrisso (for osimertinib)

Other names

crizotinib plus osimertinibosimertinib and crizotinib combination