Title: Ripretinib for treating advanced gastrointestinal stromal tumours after 3 therapies (ID3805)
Funder: Department of Health and Social Care

Abstract: Gastrointestinal stromal tumours (GIST) are a rare type of soft tissue sarcoma (a rare cancer of mesenchymal origin), which develops in the digestive tract (most frequently in the stomach and small intestine but can arise anywhere along the gastrointestinal tract). GIST are aggressive tumours and in advanced GIST the tumours will have begun to spread to other parts of the body (such as the liver or peritoneum). In over 85% of cases, the cancer cells associated with GIST are found with an activating mutation in either the tyrosine-protein kinase KIT, CD117 (KIT) or platelet derived growth factor receptor alpha (PDGFRA) gene.[1] Public Health England estimate the annual incidence of all GIST to be approximately 800 new diagnoses per year in the UK.[2] Although GIST can occur at any age, the median age at diagnosis is around 60 to 65 years.[3]_x000D_ _x000D_ The first treatment method used for GIST is surgery to remove the tumour. However drugs known as growth (kinase) inhibitors can be used to treat tumours that are too large to be removed safely, or those that have already spread to other parts of the body. There are several pharmacological options for advanced GIST._x000D_ _x000D_ NICE technology appraisal guidance 86 recommends imatinib as first-line management of people with KIT (CD117)-positive unresectable and/or KIT (CD117)-positive metastatic GIST. This guidance notes that approximately 16% of patients will experience primary resistance to imatinib, and most patients will develop a reduced response at a later stage. However, NICE technology appraisal guidance 209 does not recommend imatinib at an increased dose for people with unresectable and/or metastatic GISTs whose disease has got worse after treatment with imatinib at the standard dose of 400 mg a day. NICE technology appraisal guidance 179 recommends sunitinib as a treatment option for people with unresectable and/or metastatic GISTs whose treatment with imatinib has failed due to resistance or intolerance and NICE technology appraisal guidance 488 recommends regorafenib as a treatment option (third-line) for people with unresectable or metastatic GIST whose disease has progressed on, or who are intolerant to, prior treatment with imatinib and sunitinib, but only if their Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 1._x000D_ _x000D_ There are currently no lines of pharmacological therapy recommended specifically for the treatment of patients with GIST whose disease has progressed after treatment with third-line therapy._x000D_ _x000D_ References_x000D_ 1 Oppelt P J, Hirbe A C, Van Tine B A (2017) Gastrointestinal stromal tumors (GISTs): point mutations matter in management, a review. Journal of Gastrointestinal Oncology 8 (3) 466- 473_x000D_ 2 Detailed Statistics from the 'Get Data Out' programme NHS [online; accessed 11 February 2021]_x000D_ 3 Judson I, Bulusu R, Seddon B, Dangoor A Mudan S (2017) UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST). Clinical Sarcoma Research 7(6)

Lay abstract: To appraise the clinical and cost effectiveness of ripretinib within its marketing authorisation for people with advanced gastrointestinal stromal tumours (GIST) who have had at least 3 prior therapies.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS