In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 10033-10033
Abstract:
10033 Background: First line imatinib has improved the outcome of patients (pts) with gastrointestinal stromal tumor (GIST), but primary and secondary resistance remain a problem. Dasatinib is a second generation tyrosine kinase inhibitor (TKI) and inhibits the activity of bcr-abl, src-family kinases along with a number of other oncogenic kinases including kit. In vitro, dasatinib has shown activity against imatinib-resistant cell lines. Routinely, pts diagnosed with GIST and treated with TKIs are monitored by computed tomography (CT). 18F-fluorodeoxyglucose positron-emission-tomography (FDG-PET) measures tumor metabolic activity for early response assessment, which might be of particular use in the clinical trial setting. Methods: This two-stage phase II trial investigated dasatinib in pts with TKI-naïve GIST. Dasatinib starting dose was 2x70mg/day in pts with histologically proven, FDG-PET positive GIST. Response evaluation was done by serial CT and FDG-PET using EORTC PET response criteria (Young et al. 1999). Elective surgery was allowed after 6 months of trial treatment. Primary endpoint was response (CR+PR) by FDG-PET after one month of dasatinib. Results: 47 of planned 52 pts have been enrolled from December 2007 to November 2011, when the trial was terminated due to slow accrual. 43 pts were eligible. Median age was 61 years, 24 pts were male, 19 female and 41 had a performance status of 0 or 1. At a median follow-up of 11.9 months, 20 pts were still on treatment. Pts went off trial for elective surgery (n=6), progression (n=11), toxicity (n=3), and three patients died (one on-drug). 5% of pts experienced G4, and 38% of pts G3 toxicity, which were most often gastrointestinal or pulmonary. 28% had their dose reduced or interrupted. The primary endpoint, FDG-PET response rate (CR+PR) at 4 weeks was 67% (13 CR, 16 PR, 7 SD, 3 PD, 4 not evaluable). Median progression-free survival is 11.1 months and median overall survival not yet reached. Conclusions: Dasatinib shows promising efficacy in TKI-naïve pts with FDG-PET positive GIST. Mutational data will be presented at the meeting.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.10033
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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