Dr Kelly on the Role of Ripretinib in the GIST Treatment Paradigm

Ciara Kelly, MBBCh, BAO, interim clinical director, Sarcoma Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the current and potential roles for ripretinib (Qinlock) in the gastrointestinal stromal tumor (GIST) treatment paradigm.

On May 15, 2020, ripretinib received FDA approval as a fourth-line treatment for patients with advanced GIST who progressed on at least 3 prior kinase inhibitors, including imatinib (Gleevec). This regulatory decision was supported by data from the randomized, placebo-controlled, phase 3 INVICTUS trial (NCT03353753), in which ripretinib significantly increased median progression-free survival (PFS) from 1.0 months (95% CI, 0.9-1.7) in the placebo arm to 6.3 months (95% CI, 4.6-6.9; HR, 0.15 [95% CI, 0.09-0.25; P < .0001]), Kelly reports.

Additionally, the National Comprehensive Cancer Network Guidelines also currently recommend ripretinib for the second-line treatment of patients with advanced GIST who are intolerant to sunitinib (Sutent), Kelly adds. This recommendation is supported by findings from the phase 3 INTRIGUE trial (NCT03673501), which evaluated ripretinib vs sunitinib in the second-line setting. For patients in the KIT-mutant population, the study’s primary end point was PFS, she notes.

Results showed that the median PFS for patients with GIST harboring only mutations in KIT exon 11 and exons 13/14 was 15.0 months with sunitinib (n = 20) vs 4.0 months with ripretinib (n = 21; HR, 3.94; 95% CI, 1.71-9.11; nominal P = .0005). Furthermore, PFS outcomes with ripretinib were more favorable than those with sunitinib in patients with mutations in KIT exon 11 and exons 17/18 at 14.2 months vs 1.5 months in the ripretinib (n = 27) and sunitinib (n = 25) arms, respectively (HR, 0.22; 95% CI, 0.11-0.44; nominal P < .0001).

Importantly, ripretinib was associated with a more favorable safety profile compared with sunitinib, with fewer grade 3 and 4 adverse effects, Kelly continues. Additionally, ripretinib generated better patient-reported outcomes with respect to tolerability, she notes. These findings highlight ripretinib’s value as a treatment option for patients with GIST, particularly those who cannot tolerate other second-line therapies.