The switch-control tyrosine kinase inhibitor ripretinib (Qinlock; Deciphera Pharmaceuticals, Inc.) offers clinical benefit as fourth-line treatment in patients with advanced gastrointestinal stromal tumors, a new phase-3 study has concluded.
An international, multi-center team of researchers concluded that treatment with the novel agent improved both median overall survival and progression-free survival among these individuals, with a well-tolerated safety profile.
In an abstract presented to the 2020 Virtual Congress of the European Society for Medical Oncology (abstract 1622MO), the investigators explained that ripretinib broadly inhibits mutant KIT and PDGFRA kinase signaling. The safety and efficacy of the drug was initially established as part of the INVICTUS study (NCT03353753), which demonstrated that ripretinib significantly improved progression-free survival and yielded a clinically meaningful improvement in overall survival relative to placebo among patients with in patients with advanced gastrointestinal stromal tumors who received the drug as fourth-line therapy or greater.
“Here,” the authors wrote, “we report the updated results with an additional nine months of follow-up.”
As part of the study, participants previously treated with at least imatinib, sunitinib, and regorafenib were randomized to receive either 150 mg daily ripretinib or placebo. Patients in the placebo arm could cross over to ripretinib upon disease progression as determined by a blinded independent review committee. Moreover, all patients receiving 150 mg daily ripretinib who progressed radiographically were eligible to receive 150 mg twice-daily doses of the agent.
According to lead author John R. Zalcberg, MBBS, PhD, of Monash University in Melbourne, Australia, 129 patients were randomized, 128 of whom received treatment. Of these, 85 were treated with 150 mg daily ripretinib while the remaining 43 received placebo.
The study found that patients taking ripretinib had a median progression-free survival of 6.3 months (95% confidence interval: 4.6-8.1 months), compared with 1.0 month (95% CI: 0.9-1.7 months) for their counterparts taking placebo (hazard ratio 0.16). Median overall survival was not reached in the ripretinib arm (95% CI: 13.1-NE), compared with 6.3 months for placebo patients (95% CI: 4.1-10.0 months; HR 0.43). Ripretinib also demonstrated a confirmed objective response rate of 11.8%, compared with 0% for placebo patients.
Safety findings were consistent with the previous primary analysis results, demonstrating that ripretinib was generally well tolerated. Indeed, no new safety concerns emerged with longer exposure to the drug.
“So in conclusion,” Dr. Zalcberg said, “with an additional nine months of follow-up from the primary results of the phase-3 randomized INVICTUS trial, ripretinib continues to provide clinically meaningful benefits with a well-tolerated safety profile in patients with advanced gastrointestinal stromal tumors who have received at least three previous tyrosine kinase inhibitors.
“Of note, ripretinib is currently approved for fourth-line treatment of gastrointestinal stromal tumors in the United States, Canada, and Australia,” he added. “And enrolment in the second-line study, called INTRIGUE, which is a phase-three study comparing ripretinib versus imatinib in patients with advanced GIST, is ongoing.”