On May 15, the U.S. Food and Drug Administration (FDA) approved ripretinib (Qinlock) for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with three or more kinase inhibitors, including imatinib.
INVICTUS Trial
Efficacy was evaluated in INVICTUS, an international, multicenter, randomized, double-blind, placebo-controlled trial in 129 patients with GIST who were previously treated with imatinib, sunitinib, and regorafenib. Patients were randomly assigned 2:1 to receive ripretinib at 150 mg or placebo orally once daily until disease progression or unacceptable toxicity. Crossover was permitted at disease progression for patients assigned to receive placebo.
The major efficacy outcome measure was progression-free survival based on assessment by blinded independent central review using modified Response Evaluation Criteria in Solid Tumors, version 1.1, in which lymph nodes and bone lesions were not target lesions and a progressively growing new tumor nodule within a preexisting tumor mass must meet specific criteria to be considered unequivocal evidence of progression. Additional efficacy outcome measures included overall response rate by blinded independent central review and overall survival.
The trial demonstrated a statistically significant improvement in progression-free survival for patients in the ripretinib arm compared with those in the placebo arm (hazard ratio [HR] = 0.15, 95% confidence interval [CI] = 0.09–0.25, P < .0001). The median progression-free survival was 6.3 months (95% CI = 4.6–6.9) for ripretinib compared with 1.0 month (95% CI = 0.9–1.7) for placebo.
The overall response rate was 9% (95% CI = 4.2%–18%) in the ripretinib arm compared with 0% (95% CI = 0%–8%) in the placebo arm, though this difference was not statistically significant. The median overall survival in the ripretinib arm was 15.1 months (95% CI = 12.3–15.1) compared with 6.6 months (95% CI = 4.1–11.6) in the placebo arm, with a hazard ratio of 0.36 (95% CI = 0.21–0.62), though overall survival was not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints.
The most common adverse reactions (≥ 20%) reported with ripretinib treatment were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia, and vomiting. Other important risks of ripretinib include new primary cutaneous malignancies, hypertension, and cardiac dysfunction.
The recommended ripretinib dose is 150 mg orally once daily with or without food.
