Sunitinib treatment of pediatric metastatic GIST after failure of imatinib

Abstract

9519 Background: The genotype of most GIST in pediatric patients (pts) is “wild type” (WT-GIST), with no detectable KIT or PDGFR-α mutations. Adults with metastatic WT-GIST often have suboptimal results and primary resistance to imatinib (IM) therapy. Treatment with sunitinib malate (SU11248), an oral, multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activities, results in significant clinical benefit, such as improved survival, for adult pts with IM-resistant GIST, including WT-GIST. We report here the treatment of 3 pediatric pts with IM-resistant, metastatic GIST using sunitinib. Methods and Patients: Pt 1 presented at age 17 with numerous abdominal and hepatic GIST metastases. Following surgical debulking and 6 wks of IM treatment, objective progression was noted due to growth of omental masses and a new hepatic lesion. Pt 2 presented at age 8 with an isolated gastric GIST, fully resected, followed by adjuvant IM that continued until resection of a local recurrence 14 mos later. She had 2 more local recurrences and developed lung metastases. Pt 3 presented at age 13 with a large gastric GIST and a retroperitoneal metastasis, both fully resected and followed by adjuvant IM for 18 mos. Six mos after discontinuing IM, recurrent metastatic GIST was noted in the liver and retroperitoneum; IM therapy was resumed with stable disease for 1 yr when new hepatic lesions appeared with progression of the retroperitoneal mass. Pts 1 and 2 had WT-GIST, while genotyping of Pt 3 is pending. Sunitinib, obtained via an expanded-access protocol, was administered in 6-wk cycles, orally QD for 4 wks followed by 2 wks off dosing. Results: All pts have received 5 cycles of sunitinib. All GIST lesions have stabilized or decreased in size by CT imaging, with complete regression of 2 lung nodules in Pt 2. 18FDG-PET imaging obtained in 2 pts showed significant decreases in tumor-associated activity at all disease sites. Side effects with sunitinib have been manageable, including grade 2 GI and hematologic toxicities in pt 1, grade 3 fatigue in pt 2 and grade 3 hematologic toxicity in pt 3. Conclusions: Sunitinib shows important antitumor activity in pediatric pts with IM-resistant GIST. An expanded phase I/II trial of sunitinib in pediatric GIST is warranted. [Table: see text]