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

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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
    JournalThe Lancet
    Volume364
    Issue number9440
    DOIs
    Publication statusPublished - 25 Sept 2004

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