Impact of Imatinib Intake Timing on Oncological Outcomes in Metastatic Gastrointestinal Stromal Tumors (GISTs): A Retrospective Single-Institute Study

Background: The time-of-day administration significantly influences treatment outcomes in various cancer settings, particularly with cytotoxic chemotherapy and immunotherapy. However, data regarding tyrosine kinase inhibitors are scarce. We aimed to investigate whether the circadian timing (morning versus evening) of imatinib administration impacts progression-free survival (PFS) in patients with metastatic gastrointestinal stromal tumors (GISTs). A secondary objective was to evaluate the impact of clinical and pathological factors, such as primary tumor site and metastatic burden, on oncological outcomes. Methods: We conducted a single-center retrospective study on patients with histologically confirmed metastatic GISTs, treated with first-line imatinib (400 mg/day). Patients were categorized into "Morning" (before 12 PM) or "Evening" (after 12 PM) intake groups. The primary endpoint was PFS. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: Forty-four patients were included (median age 54.5 years). The primary tumor sites were mainly gastric n= 20 (45%) and small intestine n= 16 (36%). Hepatic metastases were present in 82% of cases (n= 36). Imatinib was administered in the morning for 59% of patients (n=26) and in the evening for 41% (n=18). Median PFS was 61.5 months in the Morning group versus 26.2 months in the Evening group. Despite this numerical difference, the analysis revealed no statistically significant difference (p=0.22). Gastric primary site (p=0.017) and low metastatic burden (p<0.01) were confirmed as significant favorable prognostic factors. Conclusion: In this cohort, no statistically significant difference in oncological outcomes was detected based on the circadian timing of Imatinib administration. While this suggests a flexible dosing schedule tailored to patient tolerance is reasonable in routine practice, larger, appropriately powered studies incorporating mutational profiling are required to definitively rule out a time-dependent therapeutic effect.