Long-term follow-up of the BFR14 trial showed that Gleevec (imatinib) remains effective in advanced gastrointestinal stromal tumors (GIST), with patients achieving complete response or full tumor removal living twice as long on average, according to findings presented at the 2025 European Society of Medical Oncology Congress (ESMO).
At a median follow-up of 219 months, 434 patients had a median overall survival 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 versus 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 re-responded to Gleevec rechallenge. Interruption at three and five 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 Gleevec area,” Dr. Quentin Devin, 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 complete response 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 Gleevec with surgery and for those treated with Gleevec alone. Age at Gleevec initiation was also identified as a predictor for 15-year survival.
Overall survival was also analyzed according to response to Gleevec and surgical intervention. Patients were grouped as complete response (CR) with Gleevec only, CR with Gleevec and surgery, partial response (PR) with Gleevec with or without surgery, stable disease (SD) after Gleevec, 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.
What is the Study Design of BFR14?
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 Gleevec. The trial's design compared Gleevec interruption to its continuation at one, three and five years.
Patients with GIST who were progression-free after three years of Gleevec 400 milligrams per day were randomly assigned to continue or interrupt Gleevec. Randomization was performed centrally and independently using computer-generated permuted blocks of two and four patients, stratified by participating center and presence or absence of residual disease on CT. The primary end point was progression-free survival. 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. Gleevec quickly became the standard first-line treatment for advanced GIST with Gleevec-sensitive mutations, though early studies reported a median overall survival of around 50 months. The very long-term impacts of Gleevec in advanced GIST remained unclear.
References
- “Twenty-Year Survival of Advanced Gastrointestinal Stromal Tumors Treated with Gleevec” by Dr. Devin, et al., ESMO Congress 2025.
- “Discontinuation of Gleevec in Patients With Advanced Gastrointestinal Stromal Tumors After 3 Years of Treatment” by Dr. Le Cesne, et al., Lancet Oncology.
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