KEY TAKEAWAYS
- This study is a phase 3 clinical trial with the acronym INTRIGUE, registered under ClinicalTrials.gov identifier NCT03673501.
- The study’s primary aim was to assess the effectiveness and safety of ripretinib and sunitinib in patients with advanced GIST.
- Patients were randomly assigned to receive either a 4-week course of ripretinib 150 mg once daily or a 4-week course of sunitinib 50 mg once daily.
- The study found that ripretinib had a higher objective response rate than sunitinib (23.9% vs 14.6%, nominal P =.03) in the KIT exon 11 ITT group.
- The study included 453 patients split evenly between the ripretinib and sunitinib groups, with 226 patients in each group in the ITT population.
- In patients with advanced GIST who had previously been treated with imatinib, ripretinib and sunitinib had similar progression-free survival, but ripretinib showed significant clinical activity.
In cases where imatinib has failed to control advanced gastrointestinal stromal tumour (GIST), the multitargeted tyrosine kinase inhibitor (TKI) sunitinib has been approved. When three or more TKIs, including imatinib, have failed to cure advanced GIST, the switch-control TKI ripretinib may be an option. In patients with advanced GIST who had previously been treated with imatinib, researchers assessed the effectiveness and safety of ripretinib and sunitinib (INTRIGUE, ClinicalTrials.gov identifier: NCT03673501). Patients with a KIT/platelet-derived growth factor mutation and intolerance to imatinib were randomly assigned to receive either a 4-week course of ripretinib 150 mg once daily or a 4-week course of sunitinib 50 mg once daily, with dosing cycles of 2 weeks on and 2 weeks off. Progression-free survival (PFS) was calculated using Response Evaluation Criteria in Solid Tumors, version 1.1 with modifications, and independent radiologic evaluation as the primary end goal. The secondary end goals were independent radiologic examination of objective response, safety, and patient-reported outcomes.
All told, 453 patients were split evenly between the ripretinib and sunitinib groups (ITT: n = 226; KIT exon 11: n = 163) and the control group (ITT: n = 227; KIT exon 11: n = 164). Compared to sunitinib (KIT exon 11 ITT), ripretinib resulted in a median progression-free survival (PFS) of 8.3 months, while sunitinib resulted in a median PFS of 7.0 months (hazard ratio, 0.88; 95% CI, 0.66 to 1.16; P =.36). Neither result warranted statistical attention. In the KIT exon 11 ITT group, ripretinib had a higher objective response rate than sunitinib (23.9% vs 14.6%, nominal P =.03). There were fewer treatment-emergent adverse events of grade 3/4 with ripretinib (41.3% v 65.6%, little P< .0001) and higher patient-reported outcomes for ripretinib’s tolerability. Compared to sunitinib, ripretinib did not improve progression-free survival. Ripretinib, on the other hand, showed significant clinical activity, reduced treatment-emergent adverse events (especially of grade 3/4 severity), and enhanced tolerance.
Source:https://pubmed.ncbi.nlm.nih.gov/35947817/
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03673501/
Bauer S, Jones RL, Blay JY, Gelderblom H, George S, Schöffski P, von Mehren M, Zalcberg JR, Kang YK, Razak AA, Trent J, Attia S, Le Cesne A, Su Y, Meade J, Wang T, Sherman ML, Ruiz-Soto R, Heinrich MC. Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Dec 1;40(34):3918-3928. doi: 10.1200/JCO.22.00294. Epub 2022 Aug 10. PMID: 35947817; PMCID: PMC9746771.
