Sunitinib in pediatric patients with advanced gastrointestinal stromal tumor: results from a phase I/II trial

Background Sunitinib is approved for treatment of adults with imatinib-resistant gastrointestinal stromal tumor (GIST) or imatinib intolerance. Methods This single-arm, multicenter, multinational phase I/II clinical trial (NCT01396148) enrolled eligible patients aged 6 to < 18 years with advanced, unresectable GIST with non-mutant KIT , or who demonstrated disease progression or intolerance to imatinib. Patients received sunitinib 15 mg/m 2 per day, 4-weeks-on/2-weeks-off (schedule 4/2), for ≤ 18 cycles over 24 months. Intra-patient dose escalation to 22.5 and subsequently 30 mg/m 2 were permitted based on individual patient tolerability and supported by real-time pharmacokinetics (PK). Primary objective was PK characterization. Secondary objectives included safety, antitumor activity and PK/pharmacodynamic relationships. Results Six patients were enrolled with median (range) age of 14 (13–16) years. All six patients completed at least three treatment cycles, with one completing all 18 cycles. Five patients had a dose increase to 22.5 mg/m 2 ; two of them had a further dose increase to 30 mg/m 2 . The average daily dose at cycle 3 was 21.1 mg/m 2 ( n = 6). Steady-state plasma concentrations were reached by day 15, cycle 1. No tumor responses were observed, but three patients had stabilization of the disease (50%). Median progression-free survival was 5.8 months (95% CI 2.3—not reached). There were no serious adverse events. Conclusions The tolerable dose of sunitinib in chemotherapy-naïve pediatric patients is at least 20 mg/m 2 on schedule 4/2. The safety profile and PK of sunitinib in pediatric patients with GIST are comparable to those in adults.