1482PD - Dasatinib first-line treatment in gastrointestinal stromal tumors. A multicenter phase II trial of the SAKK (SAKK 56/07)

Date 01 October 2012
Event ESMO Congress 2012
Session Sarcoma
Topics Anti-Cancer Agents & Biologic Therapy
Presenter Michael Montemurro
Authors M. Montemurro1, J. Domont2, P. Rutkowski3, A.D. Roth4, R. von Moos5, R. Inauen6, D. Dietrich7, C. Biaggi8, J. Prior9, S. Leyvraz10
  • 1Centre Pluridisciplinaire D'oncologie, Centre Hospitalier Universitaire Vaudois - CHUV, 1011 - Lausanne/CH
  • 2Dept. Medical Oncology, Institut Gustave Roussy, 94805 - VILLEJUIF/FR
  • 3Soft Tissue/bone Sarcoma And Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 - Warsaw/PL
  • 4Oncology, University Hospitals of Geneva, CH-1211 - Geneva/CH
  • 5Medical Oncology, Kantonal Hospital Graubünden, Chur/CH
  • 6Dept. Of Oncology, Kantonsspital St. Gallen, CH-9007 - St. Gallen/CH
  • 7Statistics, Swiss Group for Clinical Cancer Research SAKK, Bern/CH
  • 8Trial Coordination, Swiss Group for Clinical Cancer Research SAKK, Bern/CH
  • 9Nuclear Medicine, University Hospital Lausanne CHUV, Lausanne/CH
  • 10Centre Hospitalier Universitaire Vaudois - CHUV, 1011 - Lausanne/CH



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) of bcr-abl, src-family kinases and a number of other oncogenic kinases including kit. Dasatinib has shown activity against imatinib-resistant cell lines in vitro. 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.


This two-stage phase II trial investigated dasatinib in patients with histologically proven, FDG-PET positive, TKI-naïve GIST. Dasatinib starting dose was 2x70mg/day. Response evaluation was done by serial CT and FDG-PET using EORTC PET response criteria (Young et al. 1999). PET was reviewed centrally. Elective surgery was allowed after 6 months of trial treatment. Primary endpoint was response (CR + PR) by FDG-PET after one month of dasatinib.


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. 30 pts had a performance status of 0 and thirteen of 1. Mutational data are available for 28 pts so far. 20 had a KIT exon 11, one a KIT exon 9 mutation, and 7 were wild-type. At a median follow-up of 12.4 months, 15 pts were still on treatment. Pts went off trial for elective surgery (n = 6), progression (n = 13), toxicity (n = 4), other reasons (n = 2) and three patients died. 5% of pts experienced G4, and 38% of pts G3 toxicity, which were most often gastrointestinal or pulmonary. 28 pts had their dose reduced or interrupted. The primary endpoint, FDG-PET response rate (CR + PR) at 4 weeks was 72% (14 CR, 17 PR, 7 SD, 3 PD, 2 not evaluable). The response rate in patients with a KIT Exon 11 mutation was 80%, in wild-type patients 57%. Median progression-free survival is 11.1 months and median overall survival not yet reached.


Dasatinib shows promising efficacy in TKI-naïve pts with FDG-PET positive GIST.


M. Montemurro: Speakers fees and travel grants - Bayer, Pfizer, Novartis.

P. Rutkowski: Consultant - BMS, Novartis, MSD Speakers fees and travel grants - Novartis, Pfizer, MSD, BMS, Roche.

R. von Moos: Consultant/Advisor - AMGEN, Novartis, Roche, BMS, Pfizer, Merck Speakers fees - Roche, Amgen institutional Research Funds - AMGEN Expert Testimony - AMGEN.

All other authors have declared no conflicts of interest.