A recent clinical trial has demonstrated that uninterrupted use of imatinib (Gleevec) is crucial for patients with advanced gastrointestinal stromal tumors (GIST). The study, conducted in France and published in Lancet Oncology, showed that patients who stopped imatinib experienced a more rapid worsening of the disease, a shorter time until imatinib resistance, and reduced overall survival compared to those who continued the therapy. These findings reinforce expert recommendations to maintain imatinib treatment without interruption for most patients with advanced GIST.
Key Findings from the BFR14 Trial
The BFR14 trial enrolled patients with advanced GIST who were treated with imatinib for 1, 3, or 5 years. Participants whose tumors had stabilized, shrunk, or disappeared were then randomized to either continue or discontinue imatinib until disease progression. The follow-up period extended up to 20 years.
The results consistently favored uninterrupted treatment across all time points. For instance, among participants who continued imatinib after 3 years, the median overall survival was 11.2 years, compared to 8.6 years for those who stopped treatment. Similarly, progression-free survival was significantly longer in the continuous treatment groups. For those who continued imatinib after 1 year of treatment, the median progression-free survival was 27.8 months, compared with 6.1 months among participants who were assigned to stop treatment at that point.
Notably, the groups that discontinued imatinib developed resistance to the drug more quickly. For example, in the group that stopped imatinib after 1 year, the median time to resistance was 28.7 months, versus 90.6 months for the continued treatment group.
Clinical Implications and Expert Commentary
Lead investigator Jean-Yves Blay, M.D., of Centre Léon Bérard, emphasized that discontinuing imatinib should be discouraged unless there are compelling medical reasons. Ryan Denu, M.D., Ph.D., and Neeta Somaiah, M.D., of the University of Texas MD Anderson Cancer Center, echoed this sentiment in an accompanying editorial, stating, "If imatinib is working for people with advanced GIST, don’t stop a good thing."
Andrew Blakely, M.D., of NCI’s Center for Cancer Research, highlighted the importance of these findings for patient-physician communication. "Oncologists could use the new results to explain in detail why extended treatment breaks or stopping the therapy after an arbitrary time point is not usually recommended," he said.
Understanding Imatinib Resistance and Alternative Treatments
Imatinib, a tyrosine kinase inhibitor, is the standard initial treatment for advanced GIST. However, resistance to the drug eventually develops. Factors such as the cost of the drug and side effects can also limit its long-term use.
For patients who can no longer receive imatinib, newer tyrosine kinase inhibitors like sunitinib (Sutent) and nilotinib (Tasigna) are available. Treatment selection is increasingly guided by the specific genetic changes in a patient’s tumor.
Limitations and Future Directions
The researchers acknowledged a limitation of the trial was the small proportion of participants who had their tumors molecularly characterized. Further research is needed to understand the mechanisms driving resistance in patients who discontinue imatinib and to refine treatment strategies based on tumor biology.
