Updated Overall Survival and Long-Term Safety With Ripretinib Versus Sunitinib in Patients With GI Stromal Tumor: Final Overall Survival Analysis From INTRIGUE

Abstract

In the INTRIGUE phase III trial (ClinicalTrials.gov identifier: NCT03673501), adult patients with advanced gastrointestinal stromal tumor previously treated with imatinib were randomly assigned 1:1 to ripretinib 150 mg once daily or sunitinib 50 mg once daily (4 weeks on/2 weeks off). In the primary analysis, overall survival (OS) was immature. In this study, we report the final planned analysis of OS (key secondary end point), progression-free survival (PFS) on third-line therapy (second PFS; prespecified exploratory end point), and long-term safety. Final OS analysis was prespecified to occur with approximately 200 and ≥145 events in the overall and KIT exon 11 intention-to-treat (ITT) populations, respectively. As of March 15, 2023, there were 211 and 151 OS events in the overall ITT and KIT exon 11 ITT populations, respectively. Median OS was similar between second-line ripretinib and sunitinib in both populations (overall, 35.5 v 31.5 months; KIT exon 11, 35.5 v 32.8 months). Median second PFS (on third-line therapy) for the overall ITT population was similar between the ripretinib and sunitinib arms (7.7 v 7.4 months). Safety was consistent with the primary analysis. OS from this analysis was similar between arms, and second PFS suggests that receiving ripretinib did not adversely affect the PFS of third-line therapy.

FIG 1.

Final OS in the (A) overall ITT and (B) KIT exon 11 ITT populations and (C) second PFS for patients in the overall ITT population who received any third-line therapy or (D) the most common third-line therapy by random treatment assignment. Second PFS was defined as the time interval between the date of the first nonprotocol drug therapy and disease progression on this drug therapy based on local assessment or death due to any cause, whichever came first. Third-line treatment was chosen by site physicians after discontinuation of random assignment. HR, hazard ratio; ITT, intention-to-treat; NE, not estimable; OS, overall survival; PFS, progression-free survival.

FIG A1.

CONSORT diagram. AE, adverse event; IRR, independent radiologic review; ITT, intention-to-treat; PD, progressive disease.

FIG A2.

Second PFS for patients in the (A) KIT exon 11 ITT population who received any third-line treatment or (B) the most common third-line treatment by random treatment assignment. Second PFS was defined as the time interval between the date of the first nonprotocol follow-up drug therapy and the disease progression on this drug therapy based on the local assessment or death due to any cause, whichever came first. Third-line treatment was chosen by site physicians after discontinuation of random assignment. HR, hazard ratio; ITT, intention-to-treat; PFS, progression-free survival.