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 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 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; two of them had a further dose increase to 30 mg/m. The average daily dose at cycle 3 was 21.1 mg/m (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 on schedule 4/2. The safety profile and PK of sunitinib in pediatric patients with GIST are comparable to those in adults.