sunitinib + regorafenib

A dual small-molecule tyrosine kinase inhibitor regimen combining the multikinase inhibitors sunitinib and regorafenib, explored primarily in gastrointestinal stromal tumor after imatinib resistance due to heterogeneous secondary KIT mutations. Preclinical and early clinical studies indicate these agents have complementary activity across KIT resistance mutations—sunitinib is more active against ATP-binding pocket mutations (e.g., V654A), while regorafenib preferentially inhibits activation loop mutations—supporting a rapid alternation schedule (3 days sunitinib, 4 days regorafenib) to broaden subclone coverage while managing toxicity.[2][1] In a Phase Ib study of TKI-refractory GIST, the alternating regimen was feasible with a recommended phase II dose of sunitinib 37.5 mg/day and regorafenib 120 mg/day, showing tolerability without unexpected toxicities and stable disease as best response in a subset.[1][7]

Other names

sunitinib alternating with regorafenib