Efficacy of prolonged adjuvant imatinib in gastrointestinal stromal tumors: a systematic review and exploratory network meta-analysis

Background Three years of adjuvant imatinib is the established standard for patients with high-risk gastrointestinal stromal tumors (GIST), but recurrence after treatment cessation raises questions about longer treatment durations. This study evaluated evidence on extended adjuvant therapy, emphasizing treatment beyond 3 years and factors relevant to patient selection. Methods PubMed, Embase, and the Cochrane Library were searched through April 19, 2026. Randomized controlled trials, prospective single-arm studies, and cohort studies were included in the systematic review. An exploratory frequentist network meta-analysis (NMA) compared recurrence-related survival outcomes across placebo/observation and 1-, 3-, and 6-year adjuvant imatinib strategies. Results Twenty-two reports representing 13 independent studies (four randomized trials, two prospective single-arm trials, and seven cohort studies) were included. IMADGIST demonstrated improved DFS with 6 versus 3 years of imatinib (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.20–0.69; P = 0.0008). In the three-trial NMA, the 6-year strategy had the highest P-score (0.9994), with an indirect estimated HR of 0.09 (95% CI, 0.04–0.21) versus placebo/observation. However, the linear network, differences in trial populations, and distinct randomization time points limited the interpretation of indirect rankings. While 3 versus 1 year of imatinib demonstrated a long-term overall survival (OS) benefit, an additional OS benefit from treatment beyond 3 years has not been established. Molecular characteristics, recurrence risk, and tolerability were relevant to individualized treatment decisions; in PERSIST-5, 51% completed the planned 5-year course. Conclusions Extending adjuvant imatinib beyond 3 years improves recurrence-related outcomes in selected high-risk GIST patients, but the optimal duration and long-term OS effects remain uncertain. The proposed Personalized Triangle Framework integrates molecular sensitivity, recurrence risk, and tolerability as a conceptual aid rather than a validated treatment-selection algorithm. Clinical trial registration Not applicable.