Compared with sunitinib, second-line treatment with ripretinib did not improve progression-free survival in patients with gastrointestinal stromal tumor.
Treatment with ripretinib (Qinlock) in patients with gastrointestinal stromal tumor (GIST) previously treated with imatinib (Gleevec) did not demonstrate improvement in progression-free survival (PFS) compared with sunitinib (Sutent), missing the primary end point of the phase 3 INTRIGUE trial.1
Results were from 327 patients with GIST who received prior imatinib treated with either ripretinib 150 mg once daily or sunitinib 50 mg once daily, according to a press release issued by Decipher Pharmaceuticals.
“While we are disappointed with these results, which we learned yesterday, we believe this was a robust, well-designed, and well-executed study. The full results from the INTRIGUE phase 3 clinical study are expected to be presented at an upcoming medical meeting,” said Steve Hoerter, president and chief executive officer of Deciphera. “Qinlock remains the standard of care and only approved therapy in patients with fourth-line GIST, and we are committed to ensuring that patients around the world in the fourth-line GIST treatment setting have access to Qinlock.”
In the overall intent-to-treat population of the INTRIGUE study, the median PFS was 8.0 months compared with 8.3 months for the sunitinib arm (HR, 1.05; nominal P =.715). In the subgroup of patients with a KIT exon 11 primary mutation, the median PFS observed with ripretinib was 8.3 months compared with 7.0 months for the sunitinib arm (HR, 0.88; P =.360).
INTRIGUE is a phase 3, interventional, randomized, multicenter, open-label study, which enrolled a total of 426 patients with advanced GIST who progressed on or were intolerant to frontline imatinib. Aside from PFS, the study also evaluated objective response rate and overall survival as secondary end points.2
Those included were 18 years of age of older with a histologic disease diagnosis and tissue available for biopsy. Patients were required to have a molecular pathology report available, am
ECOG performance status of ≤ 2 at screening, adequate organ and bone marrow function, at least 1 measurable lesion per RECIST v1.1, and must all toxicities from frontline therapy must have been resolved to a grade 1 or lower.
Patients previously treated with any therapy other than imatinib were not permitted to enroll in the study. Further, patients who had active central nervous system metastases, class II-IV heart disease per New York Heart Association criteria, gastrointestinal abnormalities, and other comorbidities that may have interfered with study treatment were excluded from INTRIGUE.
Full results from the study will be presented during an upcoming medical meeting.
Despite the findings from ripretinib administered in the second-line setting for advanced GIST, ripretinib remains FDA approved for the treatment of adult patients with advanced GIST who had at least 3 prior lines of therapy with kinase inhibitors, including imatinib based on data from the phase 3 INVICTUS trial (NCT03353753). Ripretinib demonstrated improvement in median PFS and OS compared with placebo in the study. The most common grade 3 or 4 treatment-related treatment-emergent adverse events observed with ripretinib in INVICTUS were lipase increase (5%], hypertension (4%), fatigue (2%), and hypophosphatemia (2%).3
1. Deciphera Pharmaceuticals Announces top-line results from the intrigue phase 3 clinical study. News release. November 8, 2021. Accessed November 8, 2021. https://bit.ly/3GVcwui
2. A study of DCC-2618 vs sunitinib in advanced GIST patients after treatment with imatinib (INTRIGUE). Clinicaltrials.gov. Accessed November 8, 2021.
3. Blay JV, Serrano C, Heinrich MC, et al. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(7):923-934. doi: 10.1016/S1470-2045(20)30168-6