Imatinib Yields Durable Response, Survival Benefit in Advanced GIST

Imatinib (Gleevec) showed durable efficacy in advanced gastrointestinal stromal tumors (GIST), with complete response (CR) or complete resection yielding a twofold increase in median survival, according to long-term follow-up of the phase 3 BFR14 trial (NCT00367861) shared at the 2025 European Society of Medical Oncology Congress (ESMO).¹

At a median follow-up of 219 months, 434 patients had a median overall survival (OS) of 75.3 months, with 10-, 15-, and 20-year survival rates of 33.9%, 19.8%, and 13.1%. Female sex, gastric tumor location, smaller primary tumors, and KIT exon 11 mutations were associated with longer survival. Surgical resection of metastases with R0 margins roughly doubled median survival, and complete responses correlated with prolonged outcomes.

Patients enrolled in the second half of the study lived longer than those in the first half (86.1 months vs 60.6 months), and younger females had a median survival of 100.6 months versus 64.6 months for males.

Rapid disease progression was observed in the treatment interruption arms, but all patients demonstrated response to imatinib rechallenge. Interruption at 3 and 5 years was associated with a higher risk of developing resistance.

“This update of the BFR14 study provides important insight into the very long-term impacts of advanced GIST patients treated in the early imatinib area,” Quentin Devin MD, Lyon, France, said during the presentation. “These findings highlight the importance of striving for L0 and complete response to maximize long-term survival in metastatic GIST. Predictive tools developed from this study might help identify long-term survivors earlier. Further research should expand on these findings with a focus on the current population and integration of newer therapeutic agents.”

Predictors for achieving a CR during the trial included smaller tumors, the presence of liver-only metastases, and KIT exon 11 mutations. These factors were significant both for patients receiving imatinib with surgery and for those treated with imatinib alone. Age at imatinib initiation was also identified as a predictor for 15-year survival.

OS was also analyzed according to response to imatinib and surgical intervention. Patients were grouped as CR with imatinib only, CR with imatinib and surgery, partial response (PR) with imatinib with or without surgery, stable disease (SD) after imatinib, progressive disease (PD) as best response, and not evaluable. OS was longer in patients achieving CR regardless of treatment modality. Analysis by surgical status—no surgery, R0 (complete resection), R1 (microscopic residual), R2 (macroscopic residual), and unknown—confirmed that R0 resection was associated with improved survival.

Study Overview

The BFR14 study, initiated in 2002, is a multicenter, randomized phase 3 clinical trial that enrolled 434 patients with advanced or unresectable gastrointestinal stromal tumors treated with imatinib. The trial’s design compared imatinib interruption to its continuation at 1, 3, and 5 years.²

Patients with GIST who were progression-free after 3 years of imatinib 400 mg/day were randomly assigned to continue or interrupt imatinib. Randomization was performed centrally and independently using computer-generated permuted blocks of 2 and 4 patients, stratified by participating center and presence or absence of residual disease on CT. The primary end point was PFS. An interim analysis was planned after the first 50 patients were randomly assigned. Analyses were conducted according to the intention-to-treat principle, including all patients as assigned.

GIST was the first solid tumor in which kinase inhibitors demonstrated a survival benefit in the metastatic setting, according to study authors. Imatinib quickly became the standard first-line treatment for advanced GIST with imatinib-sensitive mutations, though early studies reported a median overall survival of around 50 months. The very long-term impacts of imatinib in advanced GIST remained unclear.

References

1. Devin Q, Blay JY, Toulmonde M, et al. Twenty-year survival of advanced gastrointestinal stromal tumours treated with imatinib: exploratory long-term follow-up of the BFR14 trial. Presented at: ESMO Congress 2025; October 17, 2025; Berlin, Germany. Abstract 2691MO
2. Le Cesne A, Ray-Coquard I, Nguyen Bui B, et al. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010;11(10):942-949. doi:10.1016/S1470-2045(10)70222-9