Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group.

PURPOSE: To evaluated the efficacy and safety of sorafenib in patients with advanced gastrointestinal stromal tumors (GIST) who failed to previous standard treatments. EXPERIMENTAL DESIGN: Thirty-one patients with measurable metastatic GIST who failed both imatinib and sunitinib were accrued. Sorafenib was administered orally at 400 mg twice daily until disease progression or development of intolerance. The primary endpoint was disease control rate (response + stable disease, DCR) at 24 weeks. RESULTS: Sorafenib was well tolerated, with hand-foot skin reaction, fatigue, hypertension, and abdominal pain being the most frequent adverse events. The relative dose intensity of sorafenib during the first 6 months was >80%. Four patients achieved partial response (response rate 13%, 95% CI 1-25%), and 16 (52%) had stable disease. DCR at 24 weeks was measured as 36% (95% CI 19-52%). Median progression-free and overall survivals were 4.9 and 9.7 months, respectively. Progression-free survival of patients with prior use of nilotinib (P = .0085) and with primary genotypes other than KIT exon 11 mutation (P = .0341) was significantly shorter than that of patients without. CONCLUSIONS: Sorafenib showed antitumor activity in this population of imatinib and sunitinib pretreated GIST. With sorafenib, about one third of patients can maintain disease control for more than 24 weeks.