Ripretinib

INVICTUS (NCT03353753) was a phase III, double-blind, placebo-controlled trial of 129 patients with advanced GISTs who had not responded to previous imatinib, sunitinib, and regorafenib therapy. Patients were randomly assigned in a 2:1 ratio to receive either ripretinib 150 mg daily (n = 85) or placebo (n = 44), with an opportunity to cross over at the time of disease progression.[41]

INVICTUS (NCT03353753) was a phase III, double-blind, placebo-controlled trial of 129 patients with advanced GISTs who had not responded to previous imatinib, sunitinib, and regorafenib therapy. Patients were randomly assigned in a 2:1 ratio to receive either ripretinib 150 mg daily (n = 85) or placebo (n = 44), with an opportunity to cross over at the time of disease progression.[41]

After a median follow-up of 6.3 months for the ripretinib arm and 1.6 months for the placebo arm, the median OS was longer for patients who received ripretinib (15.1 months), compared with patients who received placebo (6.6 months) (HR, 0.36; 95% CI, 0.21–0.62).[41][Level of evidence A1]

INVICTUS (NCT03353753) was a phase III, double-blind, placebo-controlled trial of 129 patients with advanced GISTs who had not responded to previous imatinib, sunitinib, and regorafenib therapy. Patients were randomly assigned in a 2:1 ratio to receive either ripretinib 150 mg daily (n = 85) or placebo (n = 44), with an opportunity to cross over at the time of disease progression.[41]

The median PFS was longer for patients who received ripretinib (6.3 months) than patients for who received placebo (1.0 month) (HR, 0.15; 95% CI, 0.09–0.25; P < .0001). The PFS rate at 6 months was 51% in the ripretinib arm (95% CI, 39.4%–61.4%) and 3.2% in the placebo arm (95% CI, 0.2%–13.8%).[41]

INVICTUS (NCT03353753) was a phase III, double-blind, placebo-controlled trial of 129 patients with advanced GISTs who had not responded to previous imatinib, sunitinib, and regorafenib therapy. Patients were randomly assigned in a 2:1 ratio to receive either ripretinib 150 mg daily (n = 85) or placebo (n = 44), with an opportunity to cross over at the time of disease progression.[41]

Twenty-nine patients (66%) in the placebo arm crossed over to the ripretinib arm.

INVICTUS (NCT03353753) was a phase III, double-blind, placebo-controlled trial of 129 patients with advanced GISTs who had not responded to previous imatinib, sunitinib, and regorafenib therapy. Patients were randomly assigned in a 2:1 ratio to receive either ripretinib 150 mg daily (n = 85) or placebo (n = 44), with an opportunity to cross over at the time of disease progression.[41]

Ripretinib was well tolerated. The most common grade 3 or 4 adverse events were lipase increase (5%), hypertension (4%), fatigue (2%), and hypophosphatemia (2%).

INTRIGUE (NCT03673501) was an open-label phase III trial of 453 patients with advanced GISTs who did not respond to imatinib therapy. Patients were randomly assigned to receive either ripretinib 150 mg daily (n = 226) or sunitinib 50 mg (4-weeks-on/2-weeks-off regimen; n = 227).[43]

INTRIGUE (NCT03673501) was an open-label phase III trial of 453 patients with advanced GISTs who did not respond to imatinib therapy. Patients were randomly assigned to receive either ripretinib 150 mg daily (n = 226) or sunitinib 50 mg (4-weeks-on/2-weeks-off regimen; n = 227).[43]

The median PFS did not differ between the ripretinib and sunitinib arms (8.0 months vs. 8.3 months; HR, 1.05; 95% CI, 0.82–1.33; P = .72). In addition, there was no difference in the median PFS in the KIT exon 11 cohort (8.3 months vs. 7.0 months; HR, 0.88; 95% CI, 0.66–1.16; P = .36).[43][Level of evidence B1]

INTRIGUE (NCT03673501) was an open-label phase III trial of 453 patients with advanced GISTs who did not respond to imatinib therapy. Patients were randomly assigned to receive either ripretinib 150 mg daily (n = 226) or sunitinib 50 mg (4-weeks-on/2-weeks-off regimen; n = 227).[43]

OS data were immature at the time of report.

INTRIGUE (NCT03673501) was an open-label phase III trial of 453 patients with advanced GISTs who did not respond to imatinib therapy. Patients were randomly assigned to receive either ripretinib 150 mg daily (n = 226) or sunitinib 50 mg (4-weeks-on/2-weeks-off regimen; n = 227).[43]

Patients who received ripretinib had fewer treatment-emergent adverse events (41.3% vs. 65.6%; P < .0001) and were more likely to develop drug-related grade 3 or 4 hypertension (5.8% vs. 22.6%). Dose modifications, interruptions, or discontinuations were all less common with ripretinib.

INTRIGUE (NCT03673501) was an open-label phase III trial of 453 patients with advanced GISTs who did not respond to imatinib therapy. Patients were randomly assigned to receive either ripretinib 150 mg daily (n = 226) or sunitinib 50 mg (4-weeks-on/2-weeks-off regimen; n = 227).[43]

Ripretinib did not lead to a PFS or OS benefit when compared with sunitinib. Therefore, it is not indicated unless the patient's tumor does not respond to prior lines of TKI therapy.