1418PD - Long-term outcome of dasatinib first-line treatment in gastrointestinal stromal tumors: A multicenter two stage phase II trial SAKK 56/07

Date 27 September 2014
Event ESMO 2014
Session Sarcoma
Topics Anti-Cancer Agents & Biologic Therapy
GIST
Presenter Michael Montemurro
Citation Annals of Oncology (2014) 25 (suppl_4): iv494-iv510. 10.1093/annonc/mdu354
Authors M. Montemurro1, A. Cioffi2, J. Domont3, P. Rutkowski4, A.D. Roth5, R. von Moos6, R. Inauen7, B. Bui8, R.O. Burkhard9, C. Knuesli10, S. Bauer11, P. Cassier12, H. Schwarb13, A. Le Cesne2, D. Koeberle14, D. Baertschi15, D. Dietrich16, C. Biaggi15, J. Prior17, S. Leyvraz1
  • 1Oncology, University Hospital Lausanne CHUV, 1011 - Lausanne/CH
  • 2Sarcoma Unit, Institut de cancerologie Gustave Roussy, 94805 - Villejuif/FR
  • 3Dept Of Medecine - Sarcoma Division, Institut Gustave Roussy, FR-94805 - Villejuif/FR
  • 4Soft Tissue/bone Sarcoma And Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 - Warsaw/PL
  • 5Division Of Oncology, Geneva University Hospital, 1211 - Geneva/CH
  • 6Medizinische Onkologie Und Hämatologie, Cantonal Hospital Graubünden, CH-7000 - Chur/CH
  • 7Dept. Of Oncology, Kantonsspital St. Gallen, CH-9007 - St. Gallen/CH
  • 8Medical Oncology, Institute Bergonie, 33076 - Bordeaux/FR
  • 9Onkozentrum / Oncology Center, Onkozentrum Hirslanden, CH-8032 - Zürich/CH
  • 10Medical Oncology, St. Claraspital, Basel/CH
  • 11Innere Medizin / Tumorforschung, University Hospital Essen Westdeutsches Tumorzentrum, Essen/DE
  • 12Oncology, Centre Leon Berard, 69008 - Lyon/FR
  • 13Oncology/ Internal Medicine, Kantonsspital Baden, CH-5404 - Baden/CH
  • 14Dept. Oncology/hematology, Kantonsspital St. Gallen, CH-9007 - St. Gallen/CH
  • 15Trial Coordination, Swiss Group for Clinical Cancer Research SAKK, Bern/CH
  • 16Statistics, Swiss Group for Clinical Cancer Research SAKK, Bern/CH
  • 17Nuclear Medicine, University Hospital Lausanne CHUV, Lausanne/CH

 

Abstract

Aim

Tyrosine kinase inhibitors (TKIs) have improved the outcome of patients (pts) with gastrointestinal stromal tumor (GIST), but most patients eventually develop resistance and progress. Dasatinib is a potent inhibitor of bcr-abl, kit and src-family kinases, and imatinib resistant cells, providing the rationale of this trial. Evaluation of GIST treated with TKIs is routinely done by computed tomography (CT). 18F-fluorodeoxyglucose positron-emission-tomography (FDG-PET) measures tumor metabolic activity for early response assessment and outcome prediction. Aim of this study is to evaluate the efficacy of dasatinib in TKI-naïve patients with GIST.

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. In case of progression the treatment was changed to imatinib.

Results

47 of 52 planned pts had been enrolled from December 2007 to November 2011, when the trial was terminated due to slow accrual. 42 pts were eligible. Median age was 61 years, 24 pts were male, 18 female. Performance status was 0 in 29 and 1 in 13 patients. Median follow-up (mFU) was 47.7 months. Pts went off trial for elective surgery (n=8), after 26 cycles as per protocol (n=5), progression (n=14), toxicity (n=7), other (n=5) and three patients died (two off-drug, one on-drug). Toxicity was most often gastrointestinal or pulmonary, G4 was observed in 5% of pts, and G3 in 48% of pts. Dose was interrupted or reduced in 25% of cycles. The primary endpoint, FDG-PET response rate (CR+PR) at 4 weeks was 74% (14 CR, 17 PR, 6 SD, 3 PD, 2 not evaluable). Median progression-free survival (mPFS) is 13.6 months and median overall survival (mOS) has not been reached yet.

Conclusions

Dasatinib shows high metabolic response rates in TKI-naïve pts with FDG-PET positive GIST. Toxicity was manageable at the dose studied. Median PFS was 13.6 months and 74% alive at 4 years (95% CI: 60-91%).

Disclosure

P. Rutkowski: PR has served as a member of Advisory Board and received honoraria from Novartis, BMS. All other authors have declared no conflicts of interest.