Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT

Charles Blanke, George D. Demetri, Margaret Von Mehren, Michael Heinrich, Burton Eisenberg, Jonathan A. Fletcher, Christopher Corless, Christopher D M Fletcher, Peter J. Roberts, Daniela Heinz, Elisabeth Wehre, Zariana Nikolova, Heikki Joensuu

Research output: Contribution to journalArticle

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Abstract

Purpose: The outcome of patients diagnosed with advanced gastrointestinal stromal tumor (GIST) and treated long-term with imatinib mesylate is unknown. A previous report of a randomized phase II trial of imatinib mesylate in patients with incurable GIST detailed high response rates at both the 400 and the 600 mg/d dose levels. We conducted a long-term analysis of patients treated on the trial, including patients followed during an extension phase, to evaluate survival, patterns of failure, and potential prognostic factors, including tumor mutational status. Patients and Methods: Patients with advanced GIST were enrolled onto an open-label, multicenter trial and were randomly assigned (1:1) to receive imatinib 400 versus 600 mg/d. Data were prospectively collected on KIT mutational status, total tumor area, and other potential prognostic factors. Patients were followed for a median of 63 months. Results: One hundred forty-seven patients were enrolled: 73 were in arm A (imatinib 400 mg/d), and 74 were in arm B (imatinib 600 mg/d). Response rates, median progression-free survival, and median overall survival were essentially identical on both arms, and median survival was 57 months for all patients. Forty-one patients overall (28%) remained on the drug long-term. Female sex, the presence of an exon 11 mutation, and normal albumin and neutrophil levels were independently associated with better survival. Conclusion: Nearly 50% of patients with advanced GIST who were treated with imatinib mesylate survived for more than 5 years, regardless of a 400 or 600 mg/d starting dose.

Original languageEnglish (US)
Pages (from-to)620-625
Number of pages6
JournalJournal of Clinical Oncology
Volume26
Issue number4
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

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Gastrointestinal Stromal Tumors
Survival
Imatinib Mesylate
Multicenter Studies
Disease-Free Survival
Albumins
Exons
Neoplasms
Neutrophils

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. / Blanke, Charles; Demetri, George D.; Von Mehren, Margaret; Heinrich, Michael; Eisenberg, Burton; Fletcher, Jonathan A.; Corless, Christopher; Fletcher, Christopher D M; Roberts, Peter J.; Heinz, Daniela; Wehre, Elisabeth; Nikolova, Zariana; Joensuu, Heikki.

In: Journal of Clinical Oncology, Vol. 26, No. 4, 01.02.2008, p. 620-625.

Research output: Contribution to journalArticle

Blanke, Charles ; Demetri, George D. ; Von Mehren, Margaret ; Heinrich, Michael ; Eisenberg, Burton ; Fletcher, Jonathan A. ; Corless, Christopher ; Fletcher, Christopher D M ; Roberts, Peter J. ; Heinz, Daniela ; Wehre, Elisabeth ; Nikolova, Zariana ; Joensuu, Heikki. / Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 4. pp. 620-625.
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abstract = "Purpose: The outcome of patients diagnosed with advanced gastrointestinal stromal tumor (GIST) and treated long-term with imatinib mesylate is unknown. A previous report of a randomized phase II trial of imatinib mesylate in patients with incurable GIST detailed high response rates at both the 400 and the 600 mg/d dose levels. We conducted a long-term analysis of patients treated on the trial, including patients followed during an extension phase, to evaluate survival, patterns of failure, and potential prognostic factors, including tumor mutational status. Patients and Methods: Patients with advanced GIST were enrolled onto an open-label, multicenter trial and were randomly assigned (1:1) to receive imatinib 400 versus 600 mg/d. Data were prospectively collected on KIT mutational status, total tumor area, and other potential prognostic factors. Patients were followed for a median of 63 months. Results: One hundred forty-seven patients were enrolled: 73 were in arm A (imatinib 400 mg/d), and 74 were in arm B (imatinib 600 mg/d). Response rates, median progression-free survival, and median overall survival were essentially identical on both arms, and median survival was 57 months for all patients. Forty-one patients overall (28{\%}) remained on the drug long-term. Female sex, the presence of an exon 11 mutation, and normal albumin and neutrophil levels were independently associated with better survival. Conclusion: Nearly 50{\%} of patients with advanced GIST who were treated with imatinib mesylate survived for more than 5 years, regardless of a 400 or 600 mg/d starting dose.",
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AU - Blanke, Charles

AU - Demetri, George D.

AU - Von Mehren, Margaret

AU - Heinrich, Michael

AU - Eisenberg, Burton

AU - Fletcher, Jonathan A.

AU - Corless, Christopher

AU - Fletcher, Christopher D M

AU - Roberts, Peter J.

AU - Heinz, Daniela

AU - Wehre, Elisabeth

AU - Nikolova, Zariana

AU - Joensuu, Heikki

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N2 - Purpose: The outcome of patients diagnosed with advanced gastrointestinal stromal tumor (GIST) and treated long-term with imatinib mesylate is unknown. A previous report of a randomized phase II trial of imatinib mesylate in patients with incurable GIST detailed high response rates at both the 400 and the 600 mg/d dose levels. We conducted a long-term analysis of patients treated on the trial, including patients followed during an extension phase, to evaluate survival, patterns of failure, and potential prognostic factors, including tumor mutational status. Patients and Methods: Patients with advanced GIST were enrolled onto an open-label, multicenter trial and were randomly assigned (1:1) to receive imatinib 400 versus 600 mg/d. Data were prospectively collected on KIT mutational status, total tumor area, and other potential prognostic factors. Patients were followed for a median of 63 months. Results: One hundred forty-seven patients were enrolled: 73 were in arm A (imatinib 400 mg/d), and 74 were in arm B (imatinib 600 mg/d). Response rates, median progression-free survival, and median overall survival were essentially identical on both arms, and median survival was 57 months for all patients. Forty-one patients overall (28%) remained on the drug long-term. Female sex, the presence of an exon 11 mutation, and normal albumin and neutrophil levels were independently associated with better survival. Conclusion: Nearly 50% of patients with advanced GIST who were treated with imatinib mesylate survived for more than 5 years, regardless of a 400 or 600 mg/d starting dose.

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