crizotinib + erlotinib + gefitinib + icotinib

This is a combination regimen of four small-molecule tyrosine kinase inhibitors: crizotinib, erlotinib, gefitinib, and icotinib. Crizotinib is a MET and ALK inhibitor, while erlotinib, gefitinib, and icotinib are first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. This combination targets both the EGFR pathway—commonly mutated in non-small cell lung cancer (NSCLC)—and the MET pathway, which can mediate resistance to EGFR-TKI therapy through amplification or fusion events. The rationale for combining these agents is to overcome acquired resistance in patients with EGFR-mutant NSCLC who develop secondary MET amplification or fusion after progression on prior EGFR-TKI therapy[1][3][4]. Clinical evidence supports the efficacy of combining an EGFR-TKI with crizotinib after emergence of MET-driven resistance; however, there are no reports describing simultaneous use of all four drugs together as a single regimen.

Brand names

Xalkori (crizotinib)Tarceva (erlotinib)Iressa (gefitinib)Conmana (icotinib)