Safety, efficacy and prognostic analyses of sunitinib in the post-marketing surveillance study of Japanese patients with gastrointestinal stromal tumor.

OBJECTIVE: This study was conducted to expand the sunitinib safety database in Japanese imatinib-resistant/-intolerant gastrointestinal stromal tumor patients. Retrospective analyses investigated common adverse events as potential prognostic markers. METHODS: Four hundred and seventy patients who received sunitinib between June 2008 and November 2009 were analyzed for safety, progression-free survival and overall survival; 386 for objective response rate; 88% received sunitinib on Schedule 4/2 starting at 50 mg/day. RESULTS: No unexpected safety issues occurred. Grade ≥ 3 adverse events occurred in 70%, most commonly thrombocytopenia (33%), neutropenia (22%) and leukopenia (15%). Objective response rate was 20% (95% confidence interval 16-24). Median progression-free survival was 22.4 weeks (95% confidence interval, 21.7-24.0). The overall survival rate at 24 weeks was 91% (95% confidence interval, 88-94). Higher relative dose intensity (≥70 vs. <70%) during the first 6 weeks and better Eastern Cooperative Oncology Group performance status (0 vs. ≥1) were associated with longer progression-free survival (24.0 vs. 20.1 weeks; P = 0.011; and 24.1 vs. 16.9 weeks; P < 0.001) and higher 24-week overall survival rate (94 vs. 83%; P < 0.001; and 96 vs. 83%; P < 0.001). Increased progression-free survival and overall survival rates were associated with specific adverse events. Cox proportional hazard modeling adjusted for relative dose intensity and performance status established hand-foot syndrome (hazard ratio = 0.636; 95% confidence interval, 0.456-0.888) and leukopenia (hazard ratio = 0.683; 95% confidence interval, 0.492-0.948) occurring within 12 weeks were significantly correlated with increased progression-free survival. CONCLUSION: Sunitinib showed good efficacy and tolerable safety. Factors associated with greater efficacy were relative dose intensity, performance status and specific early adverse events.