Ripretinib Provides No PFS Benefit vs Sunitinib for Patients With Advanced Gastrointestinal Stromal Tumors

There was no benefit to progress-free survival (PFS) found for patients with advanced gastrointestinal stromal tumors (GIST) treated with ripretinib compared to sunitinib, according to data from a phase 3 trial. However, ripretinib did demonstrate meaningful clinical activity, and was better tolerated. While first-line treatment with imatinib results in initial response and disease control, nearly all patients progress. As Sebastian Bauer, MD, University Hospital Essen, Essen, Germany, and colleagues wrote, “there is an unmet need for an effective broad-spectrum [tyrosine kinase inhibitor] in early treatment.”

The phase 3, interventional, multicenter, open-label INTRIGUE trial enrolled 453 patients with advanced GIST, who had progressed on or were intolerant to first-line treatment with imatinib. Patients were randomized on a 1:1 basis to either 150 mg ripretinib once daily (n = 226), or 50 mg sunitinib once daily for 4 weeks on, and 2 weeks off (n = 227). Patients were stratified by KIT/ platelet-derived growth factor α and intolerance to imatinib. The primary end point of the study was PFS, with objective response rate (ORR) and safety as secondary end points.

At the data cutoff date of September 1, 2021, the median PFS was 8.3 months in the ripretinib group compared to 8 months in the sunitinib group, which did not represent a statistically significant improvement (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.82 to 1.33; nominal P = .72). The ORR of the ripretinib group was 21.7% compared to 17.6% in the sunitinib group (nominal P = .27).

The safety profile for ripretinib was consistent with the existing information, and it was generally well-tolerated. The most common treatment-emergent adverse events were alopecia, fatigue, and myalgia. For sunitinib, the most common treatment-emergent adverse events were palmar-plantar erythrodysesthesia syndrome, diarrhea, and hypertension.

There were fewer grade 3/4 treatment-emergent adverse events in the ripretinib group (n = 92), compared to the sunitinib group (n = 145; nominal P < .0001), as well as fewer patients with grade 3/4 drug-related treatment-emergent adverse events (n = 59 for ripretinib vs n = 122 for sunitinib). There were less dose interruptions, dose reductions, and treatment discontinuations because of treatment-emergent adverse events in the ripretinib group (29.1%, 20,2%, and 3.6%, respectively) than in the sunitinib group (41.6%, 48.0%, and 7.7%).

While the primary end point of this trial was not met, Dr Bauer and colleagues noted, “PFS observed with ripretinib was comparable to PFS with sunitinib in the KIT exon 11 and intention-to-treat populations, demonstrating clinical activity of ripretinib in second-line GIST.”

Source:

Bauer S, Jones RL, Blay JY, et al. 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. Published online August 10, 2022. doi:10.1200/JCO.22.00294