Six versus three years of adjuvant imatinib in patients with localized GIST at high risk of relapse

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“Gastrointestinal stromal tumor (GIST) is the most common sarcoma and also a paradigmatic model for precision medicine in solid tumors, with the tyrosine kinase inhibitor
imatinib as a standard first-line treatment in the advanced phase and as adjuvant treatment in KIT- or PDGFRA-mutated GIST.”
Whether a longer duration of imatinib treatment improves disease-free survival (DFS) has not been explored in a randomized setting. The randomized IMADGIST study was initiated in 2014 with the aim to determine whether the prolongation of adjuvant imatinib during 3 additional years improves the outcome of high-risk GIST patients versus a standard total duration of 3 years as recommended by clinical practice guidelines. The primary endpoint was DFS. We report here the results of this clinical study.”

Figure 2 Disease-free survival in the in the 3-years and 6-years arms. (A) DFS in the entire series; (B) DFS in the stratification subgroup with a risk of relapse of 35%-70%; (C) DFS in the stratification subgroup with a risk of relapse >70%; (D) DFS in the stratification subgroup with a risk of relapse >70%, with (solid lines) or without (dotted lines) tumor rupture. CI, confidence interval; DFS, disease-free survival; Est, estimate; HR, hazard ratio; KM, Kaplan-Meier.

“The administration of imatinib in an adjuvant setting during 3 years is recommended for GIST patients at high risk of relapse in clinical practice guidelines. The IMADGIST study investigated, in a randomized controlled setting, a longer duration of adjuvant imatinib therapy for patients with high-risk GIST who had already received treatment without progression during 3 years after surgery. The results presented demonstrate that extending the adjuvant imatinib treatment from the recommended 3 years duration to 6 years results in a significant reduction in the risk of recurrence, similar in magnitude to that observed in the SSGXVIII study which defined the 3-year duration as standard.”

“The benefits of 6 years of adjuvant treatment must then be considered with a long-term perspective. The median PFS with imatinib in patients relapsing in metastatic disease
after adjuvant is 36 months, in line with other older studies. 18-23 These patients will experience subsequent progressions with a need for second, third, fourth line treatments in the long term. GIST is a life-threatening disease at this stage. This points to the importance of the prolonged maintenance of adjuvant imatinib up to 6 years, in particular in the 35%-70% risk group which benefits from a major reduction of the risk of relapse in this study”

Blay, J-Y et al. “A randomized study of 6 versus 3 years of adjuvant imatinib in patients with localized GIST at high risk of relapse.” Annals of oncology : official journal of the European Society for Medical Oncology vol. 35,12 (2024): 1157-1168. Free Full Text

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