Case Reports in Oncological Medicine / 2017 / Article / Tab 1

Case Report

Recurrent Gastrointestinal Stromal Tumors in the Imatinib Mesylate Era: Treatment Strategies for an Incurable Disease

Table 1

Institutional studies demonstrating benefit of TKI therapy for recurrent GIST.

Study designNumber of patientsPrimary endpointMain findings

Demetri et al. [30]Randomized, double-blind, placebo-controlled, multicenter, international trial comparing sunitinib versus placebo after imatinib failure321 (207 sunitinib versus 105 placebo patients)Tumor progressionMedian time to tumor progression: 27.3 weeks in patients receiving sunitinib versus 6.4 weeks with placebo

MetaGIST [31]Analysis of two large, randomized, cooperative group studies comparing two doses of IM (400 mg daily versus twice daily) in 1640 patients with advanced GISTs1640 (data analysis after 344 and 321 cases of progression or death in each study)PFS and OSHigh-dose imatinib 800 mg daily improved PFS but not OS compared to imatinib 400 mg daily

Reichardt et al. [32]Randomized phase III open-label trial comparing nilotinib versus best supportive care with advanced GIST following prior imatinib/sunitinib failure248 (2 : 1 randomization nilotinib or best supportive care)PFS, OSSubset analysis of patients with one prior regimen each of imatinib and sunitinib showed significant increase in median OS in favor of nilotinib versus best supportive care

Demetri et al. [33]Randomized, double-blinded, placebo-controlled, multicenter, international trial comparing regorafenib versus placebo after imatinib/sunitinib failure199 (133 regorafenib versus 66 placebo patients)PFSMedian PFS 4.8 months for regorafenib versus 0.9 months for placebo

Seifert et al. [34]Analysis of 85 patients with GISTs to determine expression of immune checkpoint molecules and effects of combination IM + PD-1/PD-L1 blockade in murine GISTs85 (blood samples from patients with GISTs)PD-1 receptor expression in T-cells of human GISTsThe PD-1 inhibitory receptors were upregulated on tumor-infiltrating T-cells compared with T-cells from matched blood
T-cell function in mice with GISTs treated with IM and PD-1/PD-L1 inhibitorPD-1 expression on T-cells was highest in IM-treated human GISTs
PD-1/PD-L1 blockade in vivo had no efficacy alone but enhanced antitumor effects of IM by increasing T-cell effector function

IM = imatinib mesylate, PFS = progression-free survival, OS = overall survival.