Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial

George D. Demetri, Allan T. van Oosterom, Christopher R. Garrett, Martin E. Blackstein, Manisha H. Shah, Jaap Verweij, Grant McArthur, Ian R. Judson, Michael C. Heinrich, Jeffrey A. Morgan, Jayesh Desai, Christopher D. Fletcher, Suzanne George, Carlo L. Bello, Xin Huang, Charles M. Baum, Paolo G. Casali

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    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)1329-1338
    Number of pages10
    JournalLancet
    Volume368
    Issue number9544
    DOIs
    StatePublished - Oct 14 2006

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    ASJC Scopus subject areas

    • Medicine(all)

    Cite this

    Demetri, G. D., van Oosterom, A. T., Garrett, C. R., Blackstein, M. E., Shah, M. H., Verweij, J., McArthur, G., Judson, I. R., Heinrich, M. C., Morgan, J. A., Desai, J., Fletcher, C. D., George, S., Bello, C. L., Huang, X., Baum, C. M., & Casali, P. G. (2006). Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet, 368(9544), 1329-1338. https://doi.org/10.1016/S0140-6736(06)69446-4