The treatment of metastatic gastrointestinal stromal tumor (GIST) was revolutionized with the introduction of imatinib as first-line therapy, with 60% control rates and median progression-free survival (PFS) of 27 weeks with sunitinib in the second-line setting. Neverthe less, resistance to tyrosine kinase inhibitor therapy eventually develops in the majority of patients with advanced GIST; no third-line therapy is yet approved. New data suggest that regorafenib, a unique inhibitor of several kinase-associated cancers, has a wide-range activity in this patient population (George S, et al. J Clin Oncol. 2012;30:2401-2407).
This multicenter, phase 2 clinical trial included 34 patients (33 evaluable) with metastatic and/or unresectable GIST whose disease progressed after therapy with imatinib and sunitinib. The primary end point was a composite of complete response rate, partial response rate, and stable disease after ≥16 weeks.
All patients received oral regorafenib 160 mg daily on days 1 to 21 of a 28-day cycle. After a median followup of 10.9 months, 21 patients continued to receive the drug, and 16 of them remained disease free. In addition, 5 patients continued to receive regorafenib after disease progression, because of perceived continued benefit. A total of 12 patients discontinued the study because of disease progression. Overall, the clinical benefit rate was 79%; 4 patients achieved partial response, and 22 showed stable disease after ≥16 weeks. The median PFS was 10.0 months. The most common grade 3 events were hypertension and hand-foot-skin reaction.
A phase 3 clinical trial of regorafenib versus placebo in this setting is ongoing.
