Further analysis of a subset of patients from the INVICTUS clinical trial of ripretinib (Qinlock®) showed that dose escalation may provide benefit to patients whose gastrointestinal stromal tumor (GIST) progresses.
A group of 43 patients who received 150 mg of ripretinib once daily (QD) during the clinical trial had an initial median progression-free survival (PFS) of 4.6 months. The dosage in these patients was then increased to 150 mg twice daily (BID), resulting in a secondary PFS of 3.7 months.
The median overall survival (OS) of the group receiving BID after disease progression was 18.4 months, compared to a median OS of 14.2 months in patients with disease progression who chose not to receive BID treatment. The results of the study are published in The Oncologist.
The BID dosage was well tolerated with new or worsening treatment-emergent adverse events (TEAEs) occurring in a small subset of patients: 6 (14%) experienced anemia and 3 (7%) experienced abdominal pain. A total of 7 patients discontinued BID treatment due to TEAEs.
The authors wrote “these findings from the INVICTUS study suggest that in patients with ≥fourth-line advanced GIST ripretinib [intra-patient dose escalation] to 150 mg BID after progressive disease on a ripretinib dose of 150 mg QD may provide additional clinical benefit with an acceptable safety profile.”
Ripretinib is a switch-control tyrosine kinase inhibitor shown to be effective at inhibiting mutations in the receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor α (PDGFRA) genes. The US Food and Drug Administration approved ripretinib in May 2020 as a fourth-line treatment for GIST based on the results of the pivotal phase 3 INVICTUS trial. The recommended dose is 150 mg QD with or without food.
The INVICTUS trial (NCT03353753) recruited 129 GIST patients who were randomized 2:1 to receive either 150 mg of ripretinib QD or a placebo. Patients had to have been previously treated with imatinib, sunitinib, and regorafenib. With 150 mg QD, the median PFS was 6.3 months, compared to 1 month in the placebo group.
Zalcberg JR, Heinrich MC, George S, et al. Clinical benefit of ripretinib dose escalation after disease progression in advanced gastrointestinal stromal tumor: an analysis of the INVICTUS study. Oncologist. Published online July 27, 2021. doi:10.1002/onco.13917
Phase 3 study of DCC-2618 vs placebo in advanced GIST patients who have been treated with prior anticancer therapies. US National Library of Medicine. ClinicalTrials.Gov. Accessed July 29, 2021.
Center for Drug Evaluation and Research. FDA approves ripretinib for advanced gastrointestinal stromal tumor. FDA.gov. Published May 15, 2020. Accessed July 29, 2021.