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A final analysis from the phase 3 INTRIGUE trial (NCT03673501) comparing ripretinib (Qinlock) and sunitinib malate (Sutent) revealed similar survival and safety data between the 2 agents in patients with metastatic gastrointestinal stromal tumor (GIST) who had been previously treated with imatinib (Gleevec). Results were published in the Journal of Clinical Oncology.1
In the overall intention-to-treat (ITT) population, investigators reported 211 overall survival (OS) events. The median OS was 35.5 months for patients treated with ripretinib compared with 31.5 months for patients treated with sunitinib (HR, 0.86; 95% CI, 0.65–1.13). In patients with KIT exon 11, investigators reported 151 OS events. In this subset, the median OS for ripretinib was 35.5 months vs 32.8 months for sunitinib (HR, 0.98; 95% CI, 0.71–1.34).
Median second progression-free survival (PFS), defined the time from the start of the initial study treatment (randomization) to the second instance of the disease progressing or the patient’s death from any cause, whichever happens first, was 7.7 months with ripretinib vs 7.4 months with sunitinib (HR, 1.03; 95% CI, 0.78–1.35)
Michael C. Heinrich, MD, and colleagues reported that, “Fewer patients experienced grade 3/4 treatment-emergent adverse events (TEAEs; 43% v 67%) and grade 3/4 drug-related TEAEs (27% v 58%) with ripretinib versus sunitinib, respectively.”
In particular, the most common all-grade TEAE in the total population (n = 444) was palmar-plantar erythrodysesthesia and fatigue (both at 40%). In patients treated with ripretinib, the most common all grade TEAE was alopecia (65%), whereas in patients treated with sunitinib, the most common all grade TEAE was hypertension and diarrhea (both at 48%).
Final OS analysis from INTRIGUE occurred 18 months after the primary analysis.2 At the data cutoff, OS was more mature, with an event rate of 47% compared with 22% in the primary analysis.2 Median OS from the final analysis was similar between treatment arms in both populations, and safety remained more favorable for ripretinib versus sunitinib. Second PFS across all third-line treatments was comparable between the randomly assigned arms.
In the open-label study, patients were randomly assigned 1:1 to receive 150 mg of ripretinib (n = 226) or 50 mg of sunitinib (n = 227) and remained on treatment until disease progression. Crossover was not allowed.
The investigators noted that baseline characteristics were balanced between the 2 arms with an overall median age of 60 years (range, 18-88). Further, the majority of patients were male (62.0%), White race (66.2%), and had a KIT exon 11 mutation (72.2%).
At the data cutoff of March 15, 2023, 44% of patients assigned to ripretinib and 40% to sunitinib remained on study, with 13% and 5% remaining on ripretinib and sunitinib treatment, respectively.
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Consistent with the primary analysis, ripretinib demonstrated favorable long-term safety, with more patients remaining on ripretinib vs sunitinib at the time of analysis. The consistent efficacy and favorable safety at the time of this final OS analysis further demonstrate the utility of ripretinib as second-line therapy for advanced GIST.
With 18 months of follow-up from the INTRIGUE phase 3 primary analysis, OS was similar between treatment arms in both ITT populations, and the ripretinib safety profile remained more favorable than sunitinib. The second PFS was also comparable between treatment arms in both ITT populations, suggesting that receiving second-line ripretinib did not adversely affect PFS on third-line therapy.
“These results confirm the efficacy and safety of ripretinib and demonstrate the potential benefit of ripretinib as an earlier treatment option for patients who do not tolerate treatment with sunitinib,” the investigators concluded.