Plasma trough concentration of imatinib and its effect on therapeutic efficacy and adverse events in Japanese patients with GIST

Background Imatinib mesylate (IM) is the standard chemotherapy for patients with gastrointestinal stromal tumors (GISTs) and has a favorable safety profile. Pharmacokinetics (PK), such as plasma trough concentration (Cmin), varies among patients, requiring the need for therapeutic drug monitoring (TDM) during IM administration. Despite some reports from overseas, the relationship between Cmin, adverse events (AEs), and treatment efficacy in Japanese patients with GIST has still been lacking. This study aimed to investigate the relationship between IM plasma concentration and AEs in Japanese patients with GISTs. Methods This retrospective study analyzed the data of 83 patients who underwent IM treatment for GISTs at our institution between May 2002 and September 2021. Results The IM Cmin was associated with any grade of AEs (with AEs vs. without AEs = 1294 (260–4075) vs. 857 (163–1886) ng/mL, P < 0.001), edema (with edema vs. without edema = 1278 (634–4075) vs. 1036 (163–4069) ng/mL, P = 0.017), and fatigue (with fatigue vs. without fatigue = 1373 (634–4069) vs. 1046 (163–4075) ng/mL, P = 0.044). Moreover, a Cmin ≥ 1283 ng/mL was a risk factor for severe AEs. The median progression-free survival (PFS) was 3.04 years in the lowest Cmin tertile (T1, < 917 ng/mL) compared with 5.90 years for T2 and T3 ( P = 0.010). Conclusion Edema and fatigue are potentially associated with IM plasma trough concentrations of ≥ 1283 ng/mL in Japanese patients with GISTs. Further, maintaining an IM plasma trough concentration above 917 ng/mL may improve PFS.