Definition of an Imatinib Trough Concentration Threshold in the Treatment of Advanced Gastrointestinal Stromal Tumors (Gist).

10013 Background: Imatinib (IM) as front-line treatment has dramatically changed the evolution of GIST. Demetri et al. (JCO, 0927. 3141-7) previously showed that patients with trough IM plasma concentrations (Cmin) below 1110 ng/mL (Quartile 1) had shorter time to progression. We prospectively performed routine analysis of I in advanced GIST pts in which we investigated the relationships between Cmin and progression-free survival (PFS). Methods: A clinical database of advanced GIST pts for whom Cmin measurements has been prospectively set. The concentration decile boundary that produced the most statistically significant difference in PFS for patients with Cmin values above and below the value was defined using a log-rank test. Cox regression analysis was performed to evaluate factors associated with longer PFS. Results: We evaluated 102 patients treated by IM 400 mg/day (41 stomach, 34 small bowel and 27 other or unreported primary site localizations) with 253 trough plasma determinations. Median Cmin after steady-state was 784ng/mL (range:154-3321) with 75% inter-individual and 26% intra-patient variabilities. A Cmin threshold of 1030 ng/mL was associated with longer PFS for the whole GIST population (p=0.044). However, a Cmin threshold of 780 ng/mL was found separately for stomach (p=0.043) and small bowel localizations (p=0.049). Cox regression analysis found that Cmin above 780 ng/mL was associated with 71% reduction risk of progression (p=0.008) and that small bowel localization was associated with an increased relative risk of progression of 5.31 versus stomach localization (p=0.007). Conclusions: This analysis of IM in pts treated with 400 mg/d, allowed to define a Cmin threshold of 780 ng/ml associated with 71% reduction of progression risk for stomach and small bowel localizations of advanced GIS.