Summary: Sunitinib: Approved 2nd line agent with imatinib resistance or intolerance

KIT T670I (“gatekeeper”) and V654A-sensitive to sunitinib while D842 V resistant.

Phase III: 310 patients who progressed on imatinib randomized to sunitinib or placebo. Partial response and stable disease seen in 7 and 58% of patients in the sunitinib arm while none in placebo. Median PFS was 6.3 mo with sunitinib. Improvement in OS when a novel statistical analysis was employed to account for crossover at progression.

Responses and improved PFS and OS noted in patients with WT, primary KIT exon 9, and secondary KIT exon 13 or 14.

Discontinuation of imatinib is deleterious even in the setting of disease progression.

No well-recognized mutations to explain resistance with sunitinib.