Nilotinib for treatment of gastrointestinal stromal tumors: out of the equation?

Abstract

Introduction: Imatinib, a selective tyrosine kinase inhibitor (TKI), is currently the standard treatment for unresectable and metastatic gastrointestinal stromal tumors (GISTs). However, the disease control time by imatinib is limited due to intolerance or resistance. Nilotinib, a second-generation TKI, is expected to show enhanced clinical efficacy against advanced GIST.

Areas covered: PubMed and ClincalTrial.gov were searched to identify clinical trials of nilotinib for GIST. The key words used were GIST and nilotinib and/or AMN107. This review summarizes the clinical trials of nilotinib for advanced GIST and outlines current understanding of the clinical usefulness of nilotinib in GIST therapy.

Expert opinion: Clinical trials of nilotinib for advanced GIST were readily advanced from a Phase I study to Phase III studies. Unfortunately, the clinical utility of nilotinib was not demonstrated by the randomized control trials either in patients with imatinib-resistant GIST or in patients who used nilotinib as the first-line treatment. On the basis of the trial results, nilotinib is not recommended for GIST therapy generally. Nevertheless, a comparable number of patients showed significant response with different side-effect profiles from imatinib. Thus, this new TKI may still merit attention as an important alternative to imatinib in advanced GIST patients who are intolerant to imatinib.

Keywords::

• gastrointestinal stromal tumor
• imatinib
• KIT
• molecularly targeted therapy
• nilotinib
• tyrosine kinase inhibitor

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