Ripretinib is no more effective than sunitinib but has a superior safety profile in patients with advanced gastrointestinal stromal tumors (GIST) who were previously treated with imatinib, according to results from the phase 3 INTRIGUE trial.

The median progression-free survival (PFS) was comparable with ripretinib and sunitinib, but patients receiving ripretinib were less likely to need dose modifications and experienced less deterioration in role functioning during treatment.

“Ripretinib may provide meaningful clinical benefit to patients with advanced GIST previously treated with imatinib,” said Michael C. Heinrich, MD, of Oregon Health & Science University in Portland. Dr Heinrich presented the results from INTRIGUE as an American Society of Clinical Oncology (ASCO) Plenary Series presentation.


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The phase 3 INTRIGUE trial (ClinicalTrials.gov Identifier: NCT03673501) enrolled 453 patients with advanced GIST who progressed on or were intolerant to imatinib. Patients were randomly assigned to receive ripretinib (n=226) or sunitinib (n=227). They were stratified by KIT mutational status and imatinib intolerance.

Baseline characteristics were similar between the treatment arms. Overall, the median age was 60 (range, 18-88) years, 62% of patients were men, and 66.2% were White. Most patients (72.2%) had a KIT exon 11 mutation (ex 11).

Dr Heinrich noted that ripretinib did not meet the primary endpoint of PFS superiority over sunitinib. There was no significant difference in PFS between the treatment arms for the entire cohort or among patients with ex 11.

In the entire intent-to-treat (ITT) population, the median PFS was 8.0 months with ripretinib and 8.3 months with sunitinib (hazard ratio [HR], 1.05; 95% CI, 0.82-1.33; P =.72). Among patients with ex 11 in the ITT population, the median PFS was 8.3 months and 7.0 months, respectively (HR, 0.88; 95% CI, 0.66-1.16; P =.36).

The objective response rate (ORR) was similar between the arms in the entire ITT population but superior with ripretinib among patients with ex 11. In the ex 11 ITT population, the ORR was 23.9% in the ripretinib arm and 14.6% in the sunitinib arm (difference, 9.3%; P =.03). In the entire ITT population, the ORR was 21.7% and 17.6%, respectively (difference, 4.2%; P =.27).

In both populations, the median duration of response was 16.7 months with ripretinib and 20.1 months with sunitinib.

The median treatment duration was 7.9 months in the ripretinib arm and 6.5 months in the sunitinib arm. Dose reductions were required in 19.7% and 50.2% of patients, respectively, and dose interruptions were required in 27.8% and 38.0%, respectively.

The rate of grade 3-4 treatment-emergent adverse events (TEAEs) was lower in the ripretinib arm than in the sunitinib arm — 41.3% and 65.6%, respectively — as was the rate of grade 3-4 drug-related TEAEs — 26.5% and 55.2%, respectively. 

The most common TEAE of any grade was alopecia in the ripretinib arm (64.1%) and palmar-plantar erythrodysesthesia syndrome in the sunitinib arm (51.1%). Patients in the sunitinib arm were 7 times more likely than those in the ripretinib arm to develop grade 3 palmar-plantar erythrodysesthesia syndrome and 3 times more likely to have grade 3 hypertension.

Fewer patients in the ripretinib arm experienced a “moderate to extremely large” impact of skin toxicity across treatment cycles. In addition, patients receiving ripretinib were less likely to experience deterioration in their ability to work or participate in leisure activities.

Disclosures: This research was supported by Deciphera Pharmaceuticals, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Heinrich MC, Jones RL, Gelderblom H, et al. INTRIGUE: A phase III, randomized, open-label study to evaluate the efficacy and safety of ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib. ASCO Plenary Series; January 25, 2022. Abstract 359881.