TY - JOUR
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 C.
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.
N1 - Funding Information:
We thank the patients, families, and advocates who supported this work, and the teams of research nurses and study coordinators at all centres who made this work possible. Funding for this work was provided in part by Pfizer and by a Veterans Administration Merit Review Grant (MCH) and from philanthropic support from the following sources (to GDD): The Virginia and Daniel K Ludwig Trust for Cancer Research, the Rubenstein Foundation, the Katz Foundation, the Quick Family Fund for Cancer Research, the Ronald O Perelman Fund for Cancer Research at Dana-Farber, the Stutman GIST Cancer Research Fund, and Leslie's Links. Financial support for assistance from ACUMED was provided by Pfizer.
Funding Information:
G Demetri has served as a consultant for Pfizer, Novartis, and Bristol-Myers Squibb, and has received honoraria from and provided expert testimony for Pfizer and Novartis. G McArthur has received financial compensation for a consultant role with Pfizer, research funding from Pfizer and Novartis, and speaker honoraria from Novartis. I Judson has received reimbursement from Pfizer for expenses associated with an oral presentation and an advisory board meeting. M Heinrich has received financial compensation for a consultant role with both Pfizer and Novartis and a speaker's bureau from Novartis, and research support for his institution from Pfizer and Novartis. C Bello, X Huang, and C Baum are employees of Pfizer with stock ownership. J Desai has received speaker's honoraria from Pfizer. J Morgan received travel support from Pfizer to attend a conference. P G Casali has received honoraria for lectures from Pfizer, Novartis, and Sigma-Tau, and compensation for a consultant role from Novartis. None of the other authors have potential conflicts of interest to disclose, other than the fact that the study sponsor, Pfizer, provided funds to offset the costs of participation in this study.
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<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.
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<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.
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U2 - 10.1016/S0140-6736(06)69446-4
DO - 10.1016/S0140-6736(06)69446-4
M3 - Article
C2 - 17046465
AN - SCOPUS:33749505836
SN - 0140-6736
VL - 368
SP - 1329
EP - 1338
JO - Lancet
JF - Lancet
IS - 9544
ER -