Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib

Randomised trial

Jaap Verweij, Paolo G. Casali, John Zalcberg, Axel LeCesne, Peter Reichardt, Jean Yves Blay, Rolf Issels, Allan Van Oosterom, Pancras C W Hogendoorn, Martine Van Glabbeke, Rossella Bertulli, Ian Judson

Research output: Contribution to journalArticle

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Abstract

Background Imatinib is approved worldwide for use in gastrointestinal stromal tumours (GIST). We aimed to assess dose dependency of response and progression-free survival with imatinib for metastatic GIST. Methods 946 patients were randomly allocated imatinib 400 mg either once or twice a day. Those assigned the once a day regimen who had progression were offered the option of crossover. The primary endpoint was progression-free survival. Analysis was by intention to treat. Findings At median follow-up of 760 days (IQR 644-859), 263 (56%) of 473 patients allocated imatinib once a day had progressed compared with 235 (50%) of 473 who were assigned treatment twice a day (estimated hazard ratio 0·82 [95% CI 0·69-0·98]; p=0·026). Side-effects arose in 465/470 (99%) patients allocated the once daily regimen compared with 468/472 (99%) assigned treatment twice a day. By comparison with the group treated once a day, more dose reductions (77 [16%] vs 282 [60%]) and treatment interruptions (189 [40%] vs 302 [64%]) were recorded in patients allocated the twice daily regimen, but treatment in both arms was fairly well tolerated. 52 (5%) patients achieved a complete response, 442 (47%) a partial response, and 300 (32%) stable disease, with no difference between groups. Median time to best response was 107 days (IQR 58-172). Interpretation If response induction is the only aim of treatment, a daily dose of 400 mg of imatinib is sufficient; however, a dose of 400 mg twice a day achieves significantly longer progression-free survival.

Original languageEnglish
Pages (from-to)1127-1134
Number of pages8
JournalLancet
Volume364
Issue number9440
DOIs
Publication statusPublished - Sep 25 2004

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Gastrointestinal Stromal Tumors
Disease-Free Survival
Therapeutics
Intention to Treat Analysis
Imatinib Mesylate

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Verweij, J., Casali, P. G., Zalcberg, J., LeCesne, A., Reichardt, P., Blay, J. Y., ... Judson, I. (2004). Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: Randomised trial. Lancet, 364(9440), 1127-1134. https://doi.org/10.1016/S0140-6736(04)17098-0

Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib : Randomised trial. / Verweij, Jaap; Casali, Paolo G.; Zalcberg, John; LeCesne, Axel; Reichardt, Peter; Blay, Jean Yves; Issels, Rolf; Van Oosterom, Allan; Hogendoorn, Pancras C W; Van Glabbeke, Martine; Bertulli, Rossella; Judson, Ian.

In: Lancet, Vol. 364, No. 9440, 25.09.2004, p. 1127-1134.

Research output: Contribution to journalArticle

Verweij, J, Casali, PG, Zalcberg, J, LeCesne, A, Reichardt, P, Blay, JY, Issels, R, Van Oosterom, A, Hogendoorn, PCW, Van Glabbeke, M, Bertulli, R & Judson, I 2004, 'Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: Randomised trial', Lancet, vol. 364, no. 9440, pp. 1127-1134. https://doi.org/10.1016/S0140-6736(04)17098-0
Verweij, Jaap ; Casali, Paolo G. ; Zalcberg, John ; LeCesne, Axel ; Reichardt, Peter ; Blay, Jean Yves ; Issels, Rolf ; Van Oosterom, Allan ; Hogendoorn, Pancras C W ; Van Glabbeke, Martine ; Bertulli, Rossella ; Judson, Ian. / Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib : Randomised trial. In: Lancet. 2004 ; Vol. 364, No. 9440. pp. 1127-1134.
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AU - Reichardt, Peter

AU - Blay, Jean Yves

AU - Issels, Rolf

AU - Van Oosterom, Allan

AU - Hogendoorn, Pancras C W

AU - Van Glabbeke, Martine

AU - Bertulli, Rossella

AU - Judson, Ian

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