Twenty-year survival of advanced gastrointestinal stromal tumours treated with imatinib: exploratory long-term follow-up of the BFR14 trial

Abstract

Background: Gastrointestinal stromal tumours (GIST) are driven by mutations in KIT and platelet derived growth factor receptor A (PDGFRA) kinases in >75% of patients. Imatinib, a tyrosine kinase inhibitor, has shown efficacy in metastatic GIST but the long-term survival impact remains less understood, especially after extended treatment durations.

Patients and methods: The BFR14 study, initiated in 2002, is a multicentric randomized phase III clinical trial involving 434 patients with advanced or unresectable GIST, treated with imatinib. This long-term follow-up aimed to assess the survival outcomes of the patients prospectively included in this study. Patient demographics, mutation status, overall survival (OS) and response rates were collected.

Results: With a median follow-up of 219 months, median OS was 75.3 months. Survival rates at 10, 15, and 20 years were 33.9%, 19.8%, and 13.1%, respectively. Factors significantly associated with better survival included female sex, gastric tumour location, smaller primary tumour size, and KIT exon 11 mutations. Complete response to imatinib and complete surgical resection of metastases with R0 resections are associated with a doubling of median survival and a significantly prolonged OS.

Conclusions: This long-term follow-up of the BFR14 trial shows long-term efficacy of imatinib in patients with advanced GIST. Complete resection of metastasis and achievement of complete response is associated with a doubling of median survival.

Keywords: GIST; imatinib; long term; metastasis; survival.