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 Heinrich, Jeffrey A. Morgan, Jayesh Desai, Christopher D. Fletcher, Suzanne George, Carlo L. Bello, Xin Huang, Charles M. Baum, Paolo G. Casali

    Research output: Contribution to journalArticle

    1815 Citations (Scopus)

    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

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

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    Gastrointestinal Stromal Tumors
    Randomized Controlled Trials
    Safety
    Placebos
    Neoplasms
    Protein-Tyrosine Kinases
    Multicenter Studies
    Therapeutics
    Imatinib Mesylate
    sunitinib

    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., ... 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

    Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib : a randomised controlled trial. / Demetri, George D.; van Oosterom, Allan T.; Garrett, Christopher R.; Blackstein, Martin E.; Shah, Manisha H.; Verweij, Jaap; McArthur, Grant; Judson, Ian R.; Heinrich, Michael; Morgan, Jeffrey A.; Desai, Jayesh; Fletcher, Christopher D.; George, Suzanne; Bello, Carlo L.; Huang, Xin; Baum, Charles M.; Casali, Paolo G.

    In: Lancet, Vol. 368, No. 9544, 14.10.2006, p. 1329-1338.

    Research output: Contribution to journalArticle

    Demetri, GD, van Oosterom, AT, Garrett, CR, Blackstein, ME, Shah, MH, Verweij, J, McArthur, G, Judson, IR, Heinrich, M, Morgan, JA, Desai, J, Fletcher, CD, George, S, Bello, CL, Huang, X, Baum, CM & Casali, PG 2006, 'Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial', Lancet, vol. 368, no. 9544, pp. 1329-1338. https://doi.org/10.1016/S0140-6736(06)69446-4
    Demetri, George D. ; van Oosterom, Allan T. ; Garrett, Christopher R. ; Blackstein, Martin E. ; Shah, Manisha H. ; Verweij, Jaap ; McArthur, Grant ; Judson, Ian R. ; Heinrich, Michael ; Morgan, Jeffrey A. ; Desai, Jayesh ; Fletcher, Christopher D. ; George, Suzanne ; Bello, Carlo L. ; Huang, Xin ; Baum, Charles M. ; Casali, Paolo G. / Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib : a randomised controlled trial. In: Lancet. 2006 ; Vol. 368, No. 9544. pp. 1329-1338.
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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",
    author = "Demetri, {George D.} and {van Oosterom}, {Allan T.} and Garrett, {Christopher R.} and Blackstein, {Martin E.} and Shah, {Manisha H.} and Jaap Verweij and Grant McArthur and Judson, {Ian R.} and Michael Heinrich and Morgan, {Jeffrey A.} and Jayesh Desai and Fletcher, {Christopher D.} and Suzanne George and Bello, {Carlo L.} and Xin Huang and Baum, {Charles M.} and Casali, {Paolo G.}",
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    T1 - Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib

    T2 - a randomised controlled trial

    AU - Demetri, George D.

    AU - van Oosterom, Allan T.

    AU - Garrett, Christopher R.

    AU - Blackstein, Martin E.

    AU - Shah, Manisha H.

    AU - Verweij, Jaap

    AU - McArthur, Grant

    AU - Judson, Ian R.

    AU - Heinrich, Michael

    AU - Morgan, Jeffrey A.

    AU - Desai, Jayesh

    AU - Fletcher, Christopher D.

    AU - George, Suzanne

    AU - Bello, Carlo L.

    AU - Huang, Xin

    AU - Baum, Charles M.

    AU - Casali, Paolo G.

    PY - 2006/10/14

    Y1 - 2006/10/14

    N2 - 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

    AB - 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

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