24 Mar Based on Genetic Profile, Longer Adjuvant Treatment Recommended for Some GIST Tumors
MedicalResearch.com Interview with:
Heikki Joensuu, MD
Department of Oncology
Helsinki University Hospital
University of Helsinki
MedicalResearch.com: What is the background for this study?
Response: The randomized Scandinavian Sarcoma Group (SSG) XVIII trial compared three years of adjuvant imatinib to one year of adjuvant imatinib as adjuvant treatments of patients who had undergone macroscopically complete surgery for a GIST with a high risk for tumor recurrence. In this trial, patients treated with 3 years of imatinib had improved overall survival as compared to those who were allocated to one year of adjuvant imatinib. In 2 other randomized trials that compared either 1 year of adjuvant imatinib to one year or placebo, or 2 years of adjuvant imatinib to observation, no improvement in overall survival was found, although in all three trials adjuvant imatinib improved recurrence-free survival (RFS). The reasons for the discrepant findings with respect of overall survival in the 3 trials have been unclear.
MedicalResearch.com: What are the main findings?
Response: The current study, based on the SSGXVIII trial and now published in JAMA Oncology, finds that KIT exon 11 deletion mutations that are important driver mutations and the most frequent mutational aberrations in GIST, are associated with adverse RFS in the subgroup of patients who were treated with 1 year of adjuvant imatinib, but they were not prognostic in the group of patients who received imatinib for 3 years. Similarly, high tumor mitotic counts were associated with poor RFS in the 1-year group, but not in the 3-year group.
MedicalResearch.com: What should readers take away from your report?
Response: These findings suggest that longer (3-year) adjuvant treatment with imatinib is more effective than 1-year treatment for GISTs with KIT exon 11 deletion mutation and for tumors that have a mitotic count. This helps in understanding why a longer treatment was needed to achieve an overall survival benefit.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Adjuvant treatments longer than 3 years now need to be compared to the standard 3-year treatment. Two such trials are already ongoing, one comparing 5 to 3 years, and one 6 years to 3 years.
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Joensuu H, Wardelmann E, Sihto H, Eriksson M, Sundby Hall K, Reichardt A, Hartmann JT, Pink D, Cameron S, Hohenberger P, Al-Batran S, Schlemmer M, Bauer S, Nilsson B, Kallio R, Junnila J, Vehtari A, Reichardt P. Effect of KIT and PDGFRA Mutations on Survival in Patients With Gastrointestinal Stromal Tumors Treated With Adjuvant Imatinib An Exploratory Analysis of a Randomized Clinical Trial. JAMA Oncol. Published online March 23, 2017. doi:10.1001/jamaoncol.2016.5751
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