Ripretinib is a switch-control tyrosine kinase inhibitor recently approved by the Therapeutic Goods Administration (TGA). It is indicated for the treatment of advanced gastrointestinal stromal tumours (GIST) in adults who have previously been treated with imatinib and at least two other kinase inhibitors. This approval addresses a previously unmet clinical need as there are no other approved therapies for patients with advanced or unresectable GIST who experience disease progression following treatment with imatinib, sunitinib, and regorafenib.
Ripretinib inhibits KIT proto-oncogene and platelet-derived growth factor receptor α (PDGFRA) kinase activity. Most GISTs have activating mutations in these kinases that may cause dysregulated cell growth. Ripretinib can transform the kinase into an inactive conformation which prevents downstream signalling and cell proliferation. It is also active against a broad spectrum of KIT and PDGFRA mutations.
The efficacy of ripretinib is supported by the INVICTUS study. This randomised, double-blind trial investigated ripretinib as a fourth-line agent in patients with advanced GIST. The median progression-free survival was 6.3 months in the ripretinib group, compared to 1.0 months in the placebo group. The most common adverse effects associated with ripretinib were alopecia, myalgia, nausea, fatigue, palmar-plantar erythrodysaesthesia syndrome, and diarrhoea.
- Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H. Ripretinib in patients with advanced gastrointestinal stromal tumor (GIST): a randomized, double-blind, placebo-controlled phase 3 study (INVICTUS). Lancet Oncol. 2020; 21(7): 923-34.
- Lostes-Bardaji MJ, García-Illescas D, Valverde D, Serrano C. Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward. Ther Adv Med Oncol. 2021; 13: 1758835920986498.
- Qinlock® (Ripretinib) Australian approved product information. Kew: Specialised Therapeutics. Approved December 2020.