Correlation Between Imatinib Trough Concentration and Efficacy in Advanced GIST Patients with Different Genotypes

Overview

Imatinib (IM) has significantly enhanced the prognosis of patients (pts) with advanced gastrointestinal stromal tumors (GISTs). The clinical outcomes may correlate with IM exposure. However, the efficacy threshold, particularly based on different primary KIT mutant, remains undefined. The objective of this study is to establish the efficacy threshold of imatinib (IM) plasma trough concentration (Cmin) at steady-state in Chinese patients with advanced GIST, additionally to define subgroup thresholds based on various primary KIT mutations.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The majority of GIST are driven by activating mutuations of KIT (60-70%) or platelet-derived growth factor receptor alpha (PDGFRA, 10-15%), in which KIT exon 11 mutation (52-58%) and KIT exon 9 mutation (6-9%) are the most common types of KIT mutations. Patients with different activating KIT mutations have different sensitivity to imatinib therapy. In the first-line therapy, patients with KIT exon 11 mutation receiving Imatinib with standard dose of 400mg/d has the best therapeutic effect. Patients with KIT exon 9 mutation have poor sensitivity to the standard dose of imatinib, while higher doses can lead to better outcomes. The clinical outcomes may correlate with IM exposure. However, the efficacy threshold of imatinib in Chinese patients with advanced GIST remains unclear. The investigators aim to establish the efficacy threshold of imatinib plasma trough concentration (Cmin) at steady-state in Chinese patients with advanced GIST, additionally to define subgroup thresholds based on various primary KIT mutations.

Conditions

Interventions