Starting Imatinib at 400 mg Daily in Patients with Gastrointestinal Stromal Tumors Harboring KIT Exon 9 Mutations: A Retrospective, Multicenter Study

Background Retrospective analyses suggest that patients with advanced KIT exon 9-mutated gastrointestinal stromal tumors (GISTs) receiving imatinib 800 mg (rather than 400 mg) daily have better outcomes. In the adjuvant setting, the question of the optimal dose of imatinib remains unsettled. Objective We aimed to retrospectively assess the activity of imatinib 400 mg in both the adjuvant and the advanced settings. Patients and methods We performed a multicenter study of patients with KIT exon 9-mutated GIST starting imatinib at 400 mg daily. We examined the relapse-free survival (RFS) among high-risk patients either receiving or not receiving adjuvant imatinib. In patients with advanced disease, progression-free survival (PFS, progression under imatinib 400 mg), time to imatinib failure (TIF, progression under imatinib 400, then 800 mg upon first progression), and overall survival (OS) were analyzed. Results In the post-operative setting ( n = 37), 20 patients received adjuvant imatinib. Median RFS in high-risk patients receiving adjuvant imatinib ( n = 14) was not reached (95% CI 17.5–46.6) versus 13.6 months (95% CI 4.7–13.6) for those who did not ( p = 0.37), after a median follow-up of 58 months. RFS at 36 months was 63% (30.3–96.6) versus 40% (95% CI 0–82.9), p = 0.2. In advanced disease ( n = 28), median PFS, TIF and OS were 12.7 months (95% CI 6.1–18.2), 21.0 months (95% CI 17.4–28.1) and 47.0 months (95% CI 33.5–69.2), respectively. Conclusions Despite the limitations of a retrospective analysis and the small number of patients, the benefit of adjuvant imatinib 400 mg daily in high-risk patients appeared relevant. Patients with advanced disease receiving imatinib 400 mg with subsequent dose escalation had a TIF similar to that observed with an initial dose of 800 mg. Intra-patient dose escalation in this setting might be an option.