gastrointestinal cancer

EORTC researchers discover a treatment for drug-resistant GIST

By Mary Rice, EORTC Communication Consultant

Although there are effective treatments for advanced gastrointestinal tumours (GISTs) most patients with this rare disease will eventually become resistant to them. Finding a drug that will help those patients where treatment has failed is therefore a priority. Now, for the first time, EORTC researchers have identified that the oral agent cabozantinib has clinically relevant anti-tumour activity in patients whose disease was progressing despite treatment with two other anticancer drugs. The research is published in The European Journal of Cancer.

“Based on very promising findings from my laboratory in self-made, patient-derived mouse models of GIST, we designed a multicentre European clinical trial using cabozantinib in patients who had come resistant to imatinib (Glivec) and sunitinib (Sutent),” said Professor Patrick Schöffski,  Head of the Department of General Medical Oncology, University Hospitals Leuven, and of Laboratory for Experimental Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium, who led the investigation for the EORTC Soft Tissue and Bone Sarcoma Group.

“The excellent results of this Phase 2 trial are fully in line with our preclinical data in self-made mouse models of human GIST and confirm once again the predictive character of mouse xenograft work. The working hypothesis that cabozantinib is active in advanced GIST was confirmed, as the trial met its primary endpoint, without any new safety signal detected.”

GIST is a rare tumour that occurs most commonly in the stomach or small intestine, and the most common sarcoma in the gastrointestinal tract. The tumours grow from specialised cells found in the gastrointestinal tract called interstitial cells of Cajal (ICCs). GISTs are usually found in adults aged between 40 and 70, but can also occur at younger ages, and even in children.

In the seven-country, academic, investigator-initiated clinical study, 50 patients started treatment with cabozantinib between February 2017 and August 2018. Among the first 41 who were evaluable, 24 had no worsening of disease (‘progression-free’) at week 12. At the end of the trial, the disease had been controlled in 41 of the patients, whereas in eight the disease had progressed despite treatment with cabozantinib, and one was not evaluable – an impressive disease control rate of 82%, particularly when considering the fact that patients had already failed two other established anticancer agents.

Now that clinically relevant anti-tumour activity of cabozantinib has been demonstrated in patients with advanced GIST in whom other treatments had failed, the researchers suggest that the drug should become available for such patients outside clinical trials. “The oral agent was active in all genetically-defined subsets of patients in this trial. The impressive findings of this study should be followed by a more definitive, randomised, blinded Phase 3 trial comparing cabozantinib with placebo or another available agent,” says Prof Schöffski.

 

Reference

1Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 ‘CaboGIST’”.

P. Schoffski; O. Mir; B. Kasper; Z. Papai; J-Y Blay; A. Italiano; C. Benson; K. Kopeckova; N. Ali; P. Dileo; A. LeCesne; F. Menge; S.Cousin; E.Wardelmann; A. Wozniak; S. Marreaud; S. Litiere; F. Zaffaroni; A. Nzokirantevye; I. Van den Bempt; H. Gelderblom. European Journal of Cancer, Volume 134, July 2020, Pages 62-74,https://doi.org/10.1016/j.ejca.2020.04.021

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