BACKGROUND: No effective therapeutic options for patients with unresectable imatinib-resistant gastrointestinal stromal tumour are available. We did a randomised, double-blind, placebo-controlled, multicentre, international trial to assess tolerability and anticancer efficacy of sunitinib, a multitargeted tyrosine kinase inhibitor, in patients with advanced gastrointestinal stromal tumour who were resistant to or intolerant of previous treatment with imatinib. METHODS: Blinded sunitinib or placebo was given orally once daily at a 50-mg starting dose in 6-week cycles with 4 weeks on and 2 weeks off treatment. The primary endpoint was time to tumour progression. Intention-to-treat, modified intention-to-treat, and per-protocol analyses were done. This study is registered at ClinicalTrials.gov, number NCT00075218. FINDINGS:312 patients were randomised in a 2:1 ratio to receive sunitinib (n=207) or placebo (n=105); the trial was unblinded early when a planned interim analysis showed significantly longer time to tumour progression with sunitinib. Median time to tumour progression was 27.3 weeks (95% CI 16.0-32.1) in patients receiving sunitinib and 6.4 weeks (4.4-10.0) in those on placebo (hazard ratio 0.33; p<0.0001). Therapy was reasonably well tolerated; the most common treatment-related adverse events were fatigue, diarrhoea, skin discolouration, and nausea. INTERPRETATION: We noted significant clinical benefit, including disease control and superior survival, with sunitinib compared with placebo in patients with advanced gastrointestinal stromal tumour after failure and discontinuation of imatinab. Tolerability was acceptable.
RCT Entities:
BACKGROUND: No effective therapeutic options for patients with unresectable imatinib-resistant gastrointestinal stromal tumour are available. We did a randomised, double-blind, placebo-controlled, multicentre, international trial to assess tolerability and anticancer efficacy of sunitinib, a multitargeted tyrosine kinase inhibitor, in patients with advanced gastrointestinal stromal tumour who were resistant to or intolerant of previous treatment with imatinib. METHODS: Blinded sunitinib or placebo was given orally once daily at a 50-mg starting dose in 6-week cycles with 4 weeks on and 2 weeks off treatment. The primary endpoint was time to tumour progression. Intention-to-treat, modified intention-to-treat, and per-protocol analyses were done. This study is registered at ClinicalTrials.gov, number NCT00075218. FINDINGS: 312 patients were randomised in a 2:1 ratio to receive sunitinib (n=207) or placebo (n=105); the trial was unblinded early when a planned interim analysis showed significantly longer time to tumour progression with sunitinib. Median time to tumour progression was 27.3 weeks (95% CI 16.0-32.1) in patients receiving sunitinib and 6.4 weeks (4.4-10.0) in those on placebo (hazard ratio 0.33; p<0.0001). Therapy was reasonably well tolerated; the most common treatment-related adverse events were fatigue, diarrhoea, skin discolouration, and nausea. INTERPRETATION: We noted significant clinical benefit, including disease control and superior survival, with sunitinib compared with placebo in patients with advanced gastrointestinal stromal tumour after failure and discontinuation of imatinab. Tolerability was acceptable.
Authors: Michael C Heinrich; Adrian Marino-Enriquez; Ajia Presnell; Rachel S Donsky; Diana J Griffith; Arin McKinley; Janice Patterson; Takahiro Taguchi; Cher-Wei Liang; Jonathan A Fletcher Journal: Mol Cancer Ther Date: 2012-06-04 Impact factor: 6.261
Authors: George D Demetri; Christopher R Garrett; Patrick Schöffski; Manisha H Shah; Jaap Verweij; Serge Leyvraz; Herbert I Hurwitz; Antonio Lopez Pousa; Axel Le Cesne; David Goldstein; Luis Paz-Ares; Jean-Yves Blay; Grant A McArthur; Qiang Casey Xu; Xin Huang; Charles S Harmon; Vanessa Tassell; Darrel P Cohen; Paolo G Casali Journal: Clin Cancer Res Date: 2012-06-01 Impact factor: 12.531
Authors: Huixin Yu; Neeltje Steeghs; Jacqueline S L Kloth; Djoeke de Wit; J G Coen van Hasselt; Nielka P van Erp; Jos H Beijnen; Jan H M Schellens; Ron H J Mathijssen; Alwin D R Huitema Journal: Br J Clin Pharmacol Date: 2015-05 Impact factor: 4.335
Authors: Ricardo Celestino; Jorge Lima; Alexandra Faustino; Valdemar Máximo; António Gouveia; João Vinagre; Paula Soares; José Manuel Lopes Journal: Fam Cancer Date: 2012-06 Impact factor: 2.375
Authors: Teresa S Kim; Michael J Cavnar; Noah A Cohen; Eric C Sorenson; Jonathan B Greer; Adrian M Seifert; Megan H Crawley; Benjamin L Green; Rachel Popow; Nagavarakishore Pillarsetty; Darren R Veach; Anson T Ku; Ferdinand Rossi; Peter Besmer; Cristina R Antonescu; Shan Zeng; Ronald P Dematteo Journal: Clin Cancer Res Date: 2014-02-28 Impact factor: 12.531
Authors: V R Belum; K Marulanda; C Ensslin; L Gorcey; T Parikh; S Wu; K J Busam; P A Gerber; M E Lacouture Journal: Ann Oncol Date: 2015-09-19 Impact factor: 32.976