Published online Mar 15, 2025. doi: 10.4251/wjgo.v17.i3.98746
Revised: November 2, 2024
Accepted: December 16, 2024
Published online: March 15, 2025
Processing time: 224 Days and 3.1 Hours
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.
To investigate IM plasma concentration’s role in second-line treatment decisions for c-kit 11-mutated advanced GISTs post-IM failure.
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.
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).
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.
Core Tip: This study showed that increasing the dosage of imatinib (IM) for patients with advanced gastrointestinal stromal tumors harboring c-kit exon 11 mutation who experienced failure of first-line IM treatment can prolong overall survival when the plasma concentration is < 1100 ng/mL. Switching to another tyrosine kinase inhibitor can improve the disease control rate and achieve longer progression-free survival when the plasma concentration is ≥ 1100 ng/mL. Therefore, IM plasma concentration may guide the decision-making for second-line treatment.