Managing GIST in the imatinib era: optimization of adjuvant therapy

Abstract

We reviewed studies evaluating the clinical benefits of 1 year or more of adjuvant imatinib therapy in patients with gastrointestinal stromal tumor (GIST). Data from the Scandinavian Sarcoma Group (SSG) XVIII/AIO Phase III trial of 1 year versus 3 years of adjuvant imatinib support the use of 3 years as standard of care in patients who are at high risk for GIST recurrence following resection. Although adjuvant imatinib therapy prolonged recurrence-free survival in the evaluated trials, overall survival was not significantly increased except in the SSG XVIII/AIO trial. The optimal duration of therapy, and whether high-risk patients should use adjuvant imatinib continuously, remains unknown. The importance of risk assessment, risk stratification and GIST genotype in patient selection is also discussed.

Keywords::

• adjuvant drug therapy
• gastrointestinal stromal tumor
• GIST
• imatinib mesylate
• mutational analysis

Financial & competing interests disclosure

JC Trent serves on advisory boards for Novartis, Pfizer, and GlaxoSmithKline and serves as a speaker for Novartis, Pfizer, and GlaxoSmithKline. MP Subramanian is an employee of Evidence Scientific Solutions. Medical writing support was provided by SJ Slater and L Rosenberg, CMPP of Evidence Scientific Solutions, which was supported by Novartis Pharmaceuticals Corporation. 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.

Key issues

• We reviewed trials evaluating adjuvant imatinib therapy for patients with resected gastrointestinal stromal tumors with treatment duration of at least 1 year.

• Adjuvant imatinib therapy for at least 3 years can be recommended for patients who have an intermediate or high risk of gastrointestinal stromal tumors recurrence, which is supported by current National Comprehensive Cancer Network guidelines.

• Results of the Scandinavian Sarcoma Group XVIII/AIO trial clearly demonstrate a benefit in recurrence-free and overall survival with 3 years versus 1 year of adjuvant imatinib treatment in patients at high risk of recurrence. However, the exact optimal duration of adjuvant imatinib remains unknown and is currently being evaluated in ongoing clinical trials.

• Risk of recurrence should be assessed using accepted risk assessment criteria, based on tumor size and mitotic index, to appropriately identify which patients are at greatest risk and are most likely to benefit from adjuvant imatinib therapy following surgical resection. Other factors such as gastrointestinal stromal tumors mutational status, tumor location and tumor rupture can add prognostic value.

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