A safety evaluation of imatinib mesylate in the treatment of gastrointestinal stromal tumor

ABSTRACT

Introduction: For the last 15 years, imatinib mesylate has been the first line treatment of choice for advanced (metastatic) GIST.

Areas covered: This review describes key efficacy data on imatinib for the treatment of GIST, and focuses on safety and tolerability of imatinib, with emphasis on common adverse events management and long term toxicity profile.

Expert opinion: Imatinib has been the standard of care for metastatic GIST and probably will continue to be so for the next few years. Still, despite dramatic responses initially, imatinib drug resistance continues to be the major factor for treatment discontinuation. The toxicity profile of imatinib has been well characterized, and although the majority of patients experience an adverse event during treatment with imatinib, these side effects are usually mild and manageable, with the majority of patients continuing treatment uninterruptedly. Early concerns regarding imatinib related cardiotoxicity in GIST have not been confirmed in large prospective randomized trials, with reports indicating a low incidence of approximately 0.2%-0.4%. Future strategies for treatment of imatinib resistant GIST will probably include novel tyrosine kinase inhibitors, combination therapies or immunotherapy.

KEYWORDS:

• Tyrosine kinase
• Oncogene
• kinase inhibitor
• Targeted therapy
• sarcoma

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Erratum

Declaration of Interest

GD Demetri has acted as consultant and received consulting fees from Bayer and has received research support to Dana-Farber for specific clinical trial agreements in the sarcoma unit. He has received consulting fees and acted as a consultant for Novartis and has a patent licensed to Novartis from Dana-Farber with a royalty paid to Dana-Farber. He has received consulting fees and acted as consultant and received research support to Dana-Farber for specific clinical trial agreements in the sarcoma unit from Pfizer, EMD Serono, Janssen Oncology, GlaxoSmithKline. and Sanofi Oncology. He has acted as consultant and received consulting fees from Daiichi-Sankyo, Ariad, Astra-Zeneca, ZioPharm, Polaris Pharmaceuticals and WIRB Copernicus Group. He has acted as consultant, and received scientific advisory board consulting fees and Equity (minor stake, non public) from Kolltan Pharmaceuticals. He is a member of the board of directors and received scientific advisory fees and equity (minor stake, non public) from Blueprint Medicine. He is a consultant for and received scientific advisory fees and equity (minor stake, non public) from GI therapeutics, Caris, Chapions Oncology and Bessor Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed