Long-term outcome of dasatinib first-line treatment in gastrointestinal stromal tumor: A multicenter, 2-stage phase 2 trial (Swiss Group for Clinical Cancer Research 56/07).

Michael Montemurro, Angela Cioffi, Julien Dômont, Piotr Rutkowski, Arnaud D Roth, Roger von Moos, Roman Inauen, Maud Toulmonde, Roger O Burkhard, Claudio Knuesli, Sebastian Bauer, Philippe Cassier, Heike Schwarb, Axel Le Cesne, Dieter Koeberle, Daniela Bärtschi, Daniel Dietrich, Christine Biaggi, John Prior, Serge Leyvraz

Journal: Cancer 2019;124(7):1449-1454

PMID: 29315500

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Abstract

BACKGROUND

Tyrosine kinase inhibitors (TKIs) have improved the outcome of patients with gastrointestinal stromal tumors (GISTs), but most patients eventually develop resistance and progress. Dasatinib is a potent inhibitor of BCR-ABL, KIT, and SRC family kinases as well as imatinib-resistant cells. In GISTs, response evaluation is routinely done using computed tomography (CT) and F-fluorodeoxyglucose positron emission tomography coupled to CT (FDG-PET/CT) for early response assessment and outcome prediction.

METHODS

This was a 2-stage, phase 2 trial investigating dasatinib 2 × 70 mg per day in patients with histologically proven, TKI-naïve, FDG-PET/CT-positive GIST. The primary endpoint was FDG-PET/CT response.

RESULTS

Of 52 planned patients, 47 were enrolled from January 2008 to November 2011, when the trial was terminated because of slow accrual. In total, 42 patients were eligible. The median patient age was 61 years, 24 patients were men, and 18 were women. Performance status was 0 in 29 patients and 1 in 13 patients. The median follow-up was 67.2 months. Patients went off trial for elective surgery (n = 8), after 26 cycles as per protocol (n = 5), for disease progression (n = 14), for toxicity (n = 7), and for other reasons (n = 5); and 3 patients died (2 had discontinued drug and 1 was still receiving drug). Toxicity was grade 4 in 5% and grade 3 in 48% of patients and was most often gastrointestinal or pulmonary. Dose was interrupted or reduced in 25% of cycles. The FDG-PET/CT response rate (complete plus partial responses) at 4 weeks was 74% (95% confidence interval, 56%-85%; 14 patients had a complete response, 17 had a partial response, 6 had stable disease, 3 had progressive disease, and 2 were not evaluable). The median progression-free survival was 13.6 months, and the median overall survival was not reached.

CONCLUSIONS

Address: Medical Oncology, University Hospital of Lausanne, Lausanne, Switzerland.; Medical Oncology-Sarcoma, Gustave Roussy Institute, Villejuif, France.; Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.; Division of Oncology, Geneva University Hospital, Geneva, Switzerland.; Medical Oncology and Hematology, Cantonal Hospital Graubunden, Chur, Switzerland.; Department of Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.; Medical Oncology, Bergonie Institute, Bordeaux, France.; Oncology Center, Hirslanden Hospital and Health Care, Zurich, Switzerland.; Medical Oncology, Hospital St. Claraspital, Basel, Switzerland.; Department of Medical Oncology, Sarcoma Center, West German Cancer Center, University of Duisburg-Essen, Essen, Germany.; Oncology, Leon Berard Center, Lyon, France.; Oncology/Internal Medicine, Cantonal Hospital Baden, Baden, Switzerland.; Department of Oncology/Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.; Coordinating Center, Swiss Group for Clinical Cancer Research, Bern, Switzerland.; Nuclear Medicine and Molecular Imaging, University Hospital of Lausanne, Lausanne, Switzerland.

DOI: 10.1002/cncr.31234