Rechallenge of Imatinib in GIST Having no Effective Treatment: RIGHT

Summary

The objective of this study is to compare the clinical outcomes following resumption of dosing (re-challenge) with Imatinib plus best supportive care versus placebo plus best supportive care in patients with advanced/incurable Gastrointestinal Stromal Tumors following failure of prior imatinib and sunitinib therapies.

Timeline

Start

2010-06

Primary completion

2013-03

Completion

2013-03

Outcome

Met primary endpoint

paper median PFS was 1·8 months (95% CI 1·7-3·6) with imatinib compared with 0·9 months (0·9-1·7) with placebo PMID 24140183 ↗

paper hazard ratio for progression or death 0·46, 95% CI 0·27-0·78; p=0·005 PMID 24140183 ↗

Publications

• Background Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol. 2004 Sep 15;22(18):3813-25. doi: 10.1200/JCO.2004.05.140.
• Background Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ, Kiese B, Eisenberg B, Roberts PJ, Singer S, Fletcher CD, Silberman S, Dimitrijevic S, Fletcher JA. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol. 2003 Dec 1;21(23):4342-9. doi: 10.1200/JCO.2003.04.190.
• Background Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002 Aug 15;347(7):472-80. doi: 10.1056/NEJMoa020461.
• Background De Giorgi U, Verweij J. Imatinib and gastrointestinal stromal tumors: Where do we go from here? Mol Cancer Ther. 2005 Mar;4(3):495-501. doi: 10.1158/1535-7163.MCT-04-0302.
• Background Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, Bertulli R, Judson I. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004 Sep 25-Oct 1;364(9440):1127-34. doi: 10.1016/S0140-6736(04)17098-0.
• Background Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, Blay JY, Leyvraz S, Stul M, Casali PG, Zalcberg J, Verweij J, Van Glabbeke M, Hagemeijer A, Judson I; EORTC Soft Tissue and Bone Sarcoma Group; Italian Sarcoma Group; Australasian GastroIntestinal Trials Group. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer. 2006 May;42(8):1093-103. doi: 10.1016/j.ejca.2006.01.030. Epub 2006 Apr 18.
• Background Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. doi: 10.1016/S0140-6736(06)69446-4.
• Yoo C, Ryu MH, Nam BH, Ryoo BY, Demetri GD, Kang YK. Impact of imatinib rechallenge on health-related quality of life in patients with TKI-refractory gastrointestinal stromal tumours: Sub-analysis of the placebo-controlled, randomised phase III trial (RIGHT). Eur J Cancer. 2016 Jan;52:201-8. doi: 10.1016/j.ejca.2015.10.071. Epub 2015 Dec 14.
• Kang YK, Ryu MH, Yoo C, Ryoo BY, Kim HJ, Lee JJ, Nam BH, Ramaiya N, Jagannathan J, Demetri GD. Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1175-82. doi: 10.1016/S1470-2045(13)70453-4. Epub 2013 Oct 18.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Imatinib	Small molecule	400 mg	Oral

Indications