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Combining TKIs and Immunotherapies in GIST

Insights From: Robert Hans Ingemar Andtbacka, MD, CM, Huntsman Cancer Institute ; Anthony P. Conley, MD, The University of Texas MD Anderson Cancer CenterSyma Iqbal, MD, UCS Norris Comprehensive Cancer Center and Hospital
Published: Friday, Jan 29, 2016


In the future, the treatment of patients with gastrointestinal stromal tumors (GISTs) may involve the combination of tyrosine kinase inhibitors (TKIs) with other agents that have differing mechanisms of action. The combination of immunotherapy and TKIs represents the most exciting area for current research, with promising results demonstrated in other settings. 

A phase I/II study presented at the 2015 ASCO Annual Meeting evaluated the recommended dose of imatinib, a TKI, combined with a MEK inhibitor, binimetinib. Patients enrolled into this study had, on average, three prior lines of therapy. Results established a 33% Choi partial response, and approximately 50% of participants had stable disease by RECIST 1.1 criteria, demonstrating benefit in patients who have already been heavily pretreated, states Anthony P. Conley, MD.

There are currently two combination immunotherapy studies in the phase I settings evaluating the use of ipilimumab, a monoclonal antibody that activates the immune system, with imatinib, and the combination of ipilimumab with dasatinib, another TKI. Other recent reports suggest that GISTs express high amounts of certain biomarkers, such as PD-L1, so potential strategies may also include combining anti-PD-1 or anti-PD-L1 with TKIs, says Conley.
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In the future, the treatment of patients with gastrointestinal stromal tumors (GISTs) may involve the combination of tyrosine kinase inhibitors (TKIs) with other agents that have differing mechanisms of action. The combination of immunotherapy and TKIs represents the most exciting area for current research, with promising results demonstrated in other settings. 

A phase I/II study presented at the 2015 ASCO Annual Meeting evaluated the recommended dose of imatinib, a TKI, combined with a MEK inhibitor, binimetinib. Patients enrolled into this study had, on average, three prior lines of therapy. Results established a 33% Choi partial response, and approximately 50% of participants had stable disease by RECIST 1.1 criteria, demonstrating benefit in patients who have already been heavily pretreated, states Anthony P. Conley, MD.

There are currently two combination immunotherapy studies in the phase I settings evaluating the use of ipilimumab, a monoclonal antibody that activates the immune system, with imatinib, and the combination of ipilimumab with dasatinib, another TKI. Other recent reports suggest that GISTs express high amounts of certain biomarkers, such as PD-L1, so potential strategies may also include combining anti-PD-1 or anti-PD-L1 with TKIs, says Conley.
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