Efficacy observation on imatinib reintroduction in gastrointestinal stromal tumor with high recurrence risk after imatinib adjuvant therapy failure

Abstract

To evaluate the feasibility of imatinib reintroduction in gastrointestinal stromal tumor(GIST) with high recurrence risk after imatinib adjuvant therapy failure. Clinical and follow-up data of 24 recurrent GIST patients with high recurrence risk receiving imatinib standard dose reintroduction(400 mg/d or 600 mg/d) after stopping imatinib adjuvant treatment more than 3 months in Department of GI Oncology of Peking University Cancer Hospital from August 2005 to January 2016 were retrospectively analyzed. The objective response rate(ORR), relapse-free survival(RFS) of imatinib reintroduction were evaluated and the difference of efficacy in patients receiving different imatinib adjuvant therapy duration were compared. Of 24 patients, 21 were male and 3 were female. The median age was 53 years(39-72 years). Mutation detection of tumor tissues before imatinib therapy showed 20 patients had c-Kit exon 11 mutation,3 patients exon 9 mutation and 1 patient c-Kit/PDGFRA wild type mutation. The median recurrence time was 14 months in all the patients (95%CI:7.9-20.0) and in those patients receiving imatinib adjuvant therapy for 1 or 2 years (9 patients in each group, 95%CI:11.1-16.9 and 8.2-19.8 respectively). The median recurrence time of 3 patients receiving imatinib adjuvant therapy for 3 years was 24, 41 and 54 months respectively. Of 2 patients receiving imatinib adjuvant therapy for 5 years, the median recurrence time was 4 and 18 months. Only one patient received imatinib adjuvant therapy for 6 years, and the recurrence time was 6 months. Twenty patients with exon 11 mutation and 1 patient with wide type received imatinib treatment at a dose of 400 mg daily, and 3 patients with exon 9 mutation received the dosage of 600 mg per day. Among the patients receiving imatinib reintroduction, 11 patients(45.8%) got partial response(PR), 12 patients(50.0%) had stable disease and 1 patient had progression disease. The response rate in patients receiving imatinib adjuvant therapy for 1 year(6/9, 67%) was significantly higher than that in patients receiving adjuvant therapy for ≥2 years(3/15, 20%)(P=0.036). The median progression-free survival (PFS) of imatinib reintroduction was 31 months in all the patients(95%CI:23.6-38.4). The median PFS in patients receiving imatinib adjuvant therapy for 1 year(9 cases), 2 years (9 cases) and ≥3 years (6 cases) was 50 months(95%CI:27.3-72.7), 26 months(95%CI:10.7-41.3) and fall short of median PFS. No significant difference was observed among three groups(P=0.295). Imatinib reintroduction is still effective to GIST after imatinib adjuvant therapy failure. The different imatinib adjuvant therapy duration can influence the benefit of imatinib reintroduction.