Post-hoc ctDNA analysis explains response of GIST to ripretinib versus sunitinib in the phase 3 INTRIGUE trial

The multinational phase 3 INTRIGUE study randomized adult patients with advanced GIST who had disease progression on or intolerance to imatinib to once-dail ripretinib 150 mg or sunitinib 50 mg. In the primary analysis, progression-free survival with ripretinib was not superior to sunitinib. Earlier studies showed that ripretinib and sunitinib have differential activity based on the exon location of KIT mutations. Post-hoc analysis of baseline ctDNA of phase 3 INTRIGUE patients found two mutually exclusive KIT mutations populations with differential treatment effects with ripretinib versus sunitinib. The figure shows that patients with only KIT exon 11 + 13/14 mutations had better PFS with sunitinib versus ripretinib, while patients with only KIT exon 11 + 17/18 mutations had better PFS with ripretinib versus sunitinib. The authors conclude that the analysis suggests that ctDNA analysis may improve the prediction of single-drug therapies.