A phase II study of imatinib mesylate as adjuvant treatment for curatively resected high-risk localized gastrointestinal stromal tumors

Abstract

e21515 Background: In our previous study, the presence of c-kit mutation as well as tumor size and mitotic count was an independent poor risk factor for relapse after curative resection of primary localized GIST. The patients with all the 3 poor risk factors had only 30% of 2 year relapse free survival rate (RFSR). (Kim, et al. Clin Cancer Res, 2004) It is also well known that c-kit exon 11 mutant GISTs respond better to imatinib treatment than the other mutant or wild type GISTs. Therefore, the patients who have primary localized GISTs with large size, high mitotic count, and c-kit exon 11 mutation may be the best candidate of adjuvant imatinib treatment. In this phase II study, we have evaluated the efficacy and safety of adjuvant imatinib for this patient group. Methods: Patients who underwent complete resection of a primary GIST with 1) c-kit exon 11 mutation, and 2) ≥10 mitoses/50 HPF, or tumor size ≥10 cm, or ≥5 mitoses/50 HPF and tumor size ≥5 cm were eligible. Patients received imatinib 400mg p.o. daily until recurrence of disease, intolerable toxicities, or for 2 years. The primary end point was relapse-free survival (RFS). Results: A total of 47 patients from 4 centers in Korea were enrolled. The median age was 57.0 years. Stomach was the most common primary site (n=31). Median primary tumor size was 7.5cm and median mitoses index was 12/50 HPF. With a median follow-up of 26.9 months, the median RFS and overall survival (OS) have not yet been reached. RFSR was 97.7% at 1-year and 92.7% at 2-years. Six relapses (12.8%) were documented among the 47 patients. The treatments were generally well tolerated. Grade 3–4 toxicities included neutropenia 27.7%, rash 8.5%, constipation 4.3%, anorexia 2.1%, vomiting 2.1%, and pruritis 2.1%. There were no episode of febrile neutropenia and treatment-related death. Conclusions: Postoperative adjuvant imatinib for 2 years were safe and could prolong the RFS in patients with high-risk of recurrence following complete surgical resection of the primary GIST. However, it remains unknown if this benefit in RFS can be translated into OS benefit. So, further follow-up is needed with comparison of OS with historical controls who could be use imatinib after recurrence. [Table: see text]