Significance of monitoring imatinib plasma concentration in second-line treatment decisions for c-kit 11 gene-mutated gastrointestinal stromal tumors.

Abstract

Background: For patients with advanced gastrointestinal stromal tumors (GISTs) carrying the c-kit exon 11 mutation, imatinib (IM) at a standard dosage of 400 mg per day is the preferred first-line treatment. In cases where treatment with IM fails, there is an urgent need for a more precise assessment method to determine whether to switch therapies or escalate the IM dosage. This approach will enhance clinical decision-making and optimize patient outcomes.

Aim: To investigate IM plasma concentration's role in second-line treatment decisions for c-kit 11-mutated advanced GISTs post-IM failure.

Methods: Patients with advanced GIST harboring c-kit 11 mutation who experienced failure with IM 400 mg per day as first-line treatment at our hospital were retrospectively analyzed. Patients were categorized into a low plasma (LP) concentration group (LP group, < 1100 ng/mL) and high plasma (HP) concentration group (HP group, ≥ 1100 ng/mL). Each group was further subdivided into Group A (dose-escalation group) and Group B (drug-switch group). Baseline characteristics were compared and Kaplan-Meier curves were used to analyze the survival of patients.

Results: Seventy-five patients were included in the analysis. For the LP group (n = 28), Group A (n = 14) had longer overall survival (OS) than Group B (n = 14) (P = 0.02). No differences were observed between the two subgroups in disease control rate (DCR), objective response rate, and progression-free survival (PFS) (P > 0.05). For the HP group (n = 47), Group B (n = 18) had a higher DCR and longer PFS than Group A (n = 29) (P = 0.008 and P = 0.03, respectively). No difference in OS was observed between the two subgroups (P > 0.05).

Conclusion: Increasing IM dosage for c-kit 11-mutated advanced GISTs post-IM failure may prolong OS if plasma concentration is < 1100 ng/mL. Switching tyrosine kinase inhibitors may improve DCR and PFS if ≥ 1100 ng/mL.