Skip to main content
CTOS 2024 Main banner
Final Program


Schedule at a Glance
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.
Back

(P 181) UPDATED OVERALL SURVIVAL WITH RIPRETINIB VS SUNITINIB IN PATIENTS WITH SECOND-LINE ADVANCED GASTROINTESTINAL STROMAL TUMOR AND KIT EXON 11+17/18 MUTATIONS: CIRCULATING TUMOR DNA ANALYSIS FROM INTRIGUE

Objective: Ripretinib is a switch-control tyrosine kinase inhibitor approved for patients with gastrointestinal stromal tumor (GIST) who received prior treatment with 3 or more kinase inhibitors, including imatinib. Sunitinib is approved for advanced GIST after imatinib failure. In an exploratory analysis of baseline circulating tumor DNA (ctDNA) from the INTRIGUE trial, patients with primary mutations in KIT exon 11 and secondary mutations exclusively in KIT exons 17/18 (KIT exon 11 + 17/18) received clinical benefit from ripretinib but not sunitinib (Heinrich MC, et al. Nat Med. 2024). Here, we present final overall survival (OS) and updated safety in patients with KIT exon 11 + 17/18 mutations from INTRIGUE.

Methods: INTRIGUE (NCT03673501) is an open-label, phase 3 study of adults with advanced GIST who had disease progression on or intolerance to imatinib. Randomization was 1:1 to ripretinib 150 mg once daily (QD) or sunitinib 50 mg QD (4 weeks on/2 weeks off). Final OS analysis was prespecified to occur with ≥200 and ≥145 events in the all-patient intent-to-treat (ITT) and KIT exon 11 ITT populations, respectively. Baseline peripheral whole blood was analyzed by Guardant360®, a 74-gene ctDNA next-generation sequencing–based assay. Data cutoff was March 15, 2023.

Results: Of 453 patients, ctDNA was analyzed in an exploratory analysis for 362; 52 had mutations exclusively in KIT exon 11 + 17/18 (ripretinib, n = 27; sunitinib, n = 25). Patients with KIT exon 11 + 17/18 mutations had better OS with ripretinib vs sunitinib (median, not reached vs 17.5 months; hazard ratio, 0.37; 95% CI, 0.17 to 0.80; nominal P = 0.0091). Fewer of these patients had grade 3/4 drug-related treatment-emergent adverse events and serious adverse events with ripretinib vs sunitinib (33% vs 50% and 4% vs 13%, respectively). Median treatment duration in these patients for ripretinib vs sunitinib was 15.6 vs 3.0 months.

Conclusion: In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for patients with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was consistent and more favorable for ripretinib vs sunitinib in these patients. Previously presented at the 2024 ESMO Sarcoma and Rare Cancers Congress.