The following is a summary of “Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial” published in the December 2022 issue of Oncology by Bauer et al.

After imatinib failed to treat advanced gastrointestinal stromal tumors (GIST), the multitargeted tyrosine kinase inhibitor (TKI) sunitinib was authorized. After receiving three or more TKIs, including imatinib, in the past, including advanced GIST, ripetinib is a switch-control TKI that has been authorized for use. In patients with advanced GIST who had previously had imatinib treatment, researchers assessed the effectiveness and safety of ripretinib vs sunitinib.

About 1:1 or Once-daily ripretinib 150 mg or once-daily sunitinib 50 mg  (4 weeks on/2 weeks off) were randomly assigned to patients, stratified by imatinib intolerance and KIT/platelet-derived growth factor α mutation. The main outcome was progression-free survival (PFS), which was determined by independent radiologic evaluation using version 1.1 of the modified Response Evaluation Criteria in Solid Tumors. Safety, patient-reported outcome measures, and objective response rate by independent radiologic evaluation were secondary end objectives.

Overall, 453 individuals received either sunitinib (ITT, n = 227; KIT exon 11 ITT, n = 164) or ripretinib (ITT, n = 226; KIT exon 11 ITT, n = 163) at random. Riprotinib and sunitinib had median PFS of 8.3 and 7.0 months, respectively (KIT exon 11 ITT; hazard ratio, 0.88; 95% CI, 0.66 to 1.16; P=.36); ripretinib and sunitinib had median PFS (ITT) of 8.0 and 8.3 months, respectively ( hazard ratio, 1.05; 95% CI, 0.82 to 1.33; nominal P =.72 They were both not statistically significant. In the KIT exon 11 ITT group, the objective response rate was greater for ripretinib compared to sunitinib (23.9% v 14.6%, nominal P =.03). Ripretinib was linked to a superior safety profile, fewer grade 3/4 treatment-emergent adverse events (41.3% v 65.6%, nominal P<.0001), and higher ratings on patient-reported outcome measures of tolerance.

Regarding PFS, ripetinib wasn’t better than sunitinib. However, ripretinib showed significant clinical activity, fewer grade 3/4 treatment-emergent adverse events, and improved tolerability.