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Intra-patient dose escalation of ripretinib to 150 mg twice a day following disease progression extended progression-free survival for patients with advanced gastrointestinal stromal tumor after receiving fourth-line therapy.
Intra-patient dose escalation (IPDE) of ripretinib (Qinlock) to 150 mg twice daily following disease progression extended progression-free survival (PFS) for patients with advanced gastrointestinal stromal tumor (GIST) after receiving fourth-line therapy, according to findings presented the data in a poster on the first day of the 2021 American Society of Clinical Oncology Annual Meeting.1
“Based on this exploratory analysis of the phase 3 INVICTUS study, ripretinib dose escalated to 150 mg BID after disease progression on ripretinib 150 mg QD provided clinical benefits for patients with advanced GIST receiving more than fourth line therapy,” said John R. Zalcberg, MBBS, PhD, lead author and head of cancer research at Monash University in Melbourne, Australia.
These findings provide another treatment option for patients who have received ripretinib in the fourth line, he added.
In the INVICTUS study (NCT03353753), investigators enrolled 129 patients previously treated with 3 or more prior tyrosine kinase inhibitors (TKIs), including imatinib (Gleevec), sunitinib (Sutent), or regorafenib (Stivarga) into the double-blind, placebo-controlled study. Patients were randomly assigned to either ripretinib at a starting dose of 150 mg once daily (n = 85) or placebo (n = 44) in fourth line and received treatment until progressive disease.
In this analysis (data cutoff of August 10, 2020), 43 patients in the IPDE arm received ripretinib at 150 mg once a day and were then escalated to 150 mg twice a day. Among these patients, the median PFS was 4.6 months (95% CI, 2.7-6.4) during the once-a-day treatment period (PFS1). “When dose escalation occurred, the median PFS was 3.7 months, which gave a PFS1 to PFS2 ratio of 80%,” Zalcberg said.
The median duration of treatment in the IPDE arm of patients receiving ripretinib 150 mg twice a day was 3.7 months. Between the once-a-day and twice-a-day periods, 37.2% of patients were on treatment for 12 months or more.
The median overall survival (OS) was 18.4 months in the IPDE arm compared with 14.2 months for those who did not proceed to dose escalation (HR, 0.74; 95% CI, 0.37-1.49). The median OS was 18.2 months in the INVICTUS intent-to-treat population compared with 6.3 months for those assigned to placebo (HR, 0.42; 95% CI, 0.27-0.67).
Zalcberg said the IPDE dose was well tolerated. The only new or worsening grade 3/4 treatment-emergent adverse events were anemia in 6 patients (14%) and abdominal pain in 3 (7%).
The FDA approved ripretinib in May 2020 as the first therapy specifically approved for the fourth-line treatment of patients with GIST. In findings from INVICTUS, the agent demonstrated a statistically significant improvement in PFS compared with placebo (HR, 0.15; 95% CI, 0.09-0.25; P < .0001).2
In an updated analysis of the trial presented at the Connective Tissue Oncology Society (CTOS) 2020 virtual meeting in November 2020, investigators noted that ripretinib continued to demonstrate a clinically meaningful benefit as well as a tolerable safety profile.3
Specifically, patients assigned to ripretinib had a median PFS of 6.3 months vs 1.0 month for patients who received placebo (HR, 0.16; 95% CI, 0.1-0.27).