Phase 2 Study of Nilotinib As Third-line Therapy for Patients with Gastrointestinal Stromal Tumor

Background: Patients with gastrointestinal stromal tumors (GISTs) resistant to both imatinib and sunitinib have a poor prognosis and few therapeutic options. In this study, the efficacy and safety of nilotinib (AMN107) as a third-line therapy for patients with GISTs was evaluated.

Methods: A single-arm, open-label trial was conducted in 8 Japanese hospitals. The key eligibility criteria included resistance or intolerance to both imatinib and sunitinib treatment. The primary endpoint was disease control rate, defined as the percentage of patients with complete response, partial response (PR), or stable disease (SD) lasting 24 weeks or longer.

Results: Thirty-five patients were enrolled and treated with nilotinib 400 mg twice daily, which generally was well tolerated. Disease control rate at Week 24 was 29% (90% confidence interval, 16.4%-43.6%). The median progression-free survival was 113 days, and the median overall survival was 310 days. The objective response rate was 3%, comprising 1 PR in a patient with a GIST possessing both a KIT exon 11 mutation, and an imatinib-resistant and sunitinib-resistant KIT exon 17 mutation. Twenty-three (66%) patients had SD (≥6 weeks) as the best response.

Conclusions: These results suggest that nilotinib is generally well tolerated and has encouraging antitumor activity in patients with GIST who failed both imatinib and sunitinib.