Standard versus personalized schedule of regorafenib in metastatic gastrointestinal stromal tumors (GIST): A retrospective, multicenter, real-world study.

Abstract

e23521 Background: Regorafenib (REG) is a multikinase inhibitor approved as third-line treatment in gastrointestinal stromal tumors (GIST). Although its proven activity, REG can present a relevant adverse profile which often leads to treatment modifications and transient or permanent discontinuation; thus, in clinical practice physicians usually adopt various dosing and interval schedules to counteract REG-related adverse events (AEs) and avoid treatment interruption. The aim of this real-world study was to investigate the efficacy and safety of personalized schedules of REG in metastatic GIST patients, in comparison with the standard schedule (160 mg daily, 3-weeks-on, 1-week-off schedule). Methods: Institutional registries across seven Italian reference centers were retrospectively reviewed and data of interest retrieved to identify GIST patients who had received REG from February 2013 to January 2021. The primary endpoint was Progression-Free Survival (PFS), with Overall Survival (OS) also assessed as secondary endpoint. The Kaplan-Meier method was used to estimate survival and the log-rank test to make comparisons. The impact of variables on survival was assessed through univariate and multivariate analysis. Results: A total of 152 GIST patients (82 male and 70 female) were included and split in two groups on the basis of the REG treatment plan received (standard vs personalized). Among the 103 patients for whom the treatment was personalized (38 since the beginning and 65 during the treatment course), the main strategies adopted were the following: 120 mg/day d1-21 e28 (n = 56; 54.4%); 80 mg/day d1-21 e28 (n = 22; 21.4%); 160 mg/day d1-5 e7 (n = 13; 12.6%). At a median follow-up of 36.5 months, median Overall Survival (OS) was 16.6 months (95% CI 14.1-21.8) and 20.5 months (95% CI 15.0-25.4) in the standard-dose and the personalized schedule groups, respectively (HR 0.75; 95% CI 0.49-1.22; p = 0.16). Median Progression-Free Survival (PFS) was 5.6 months (95% CI 3.3-not reached) and 9.7 months (95% CI 7.9-14.5) in the same groups (HR 0.51; 95% CI 0.34-0.75; p = 0.00052). Conclusions: Despite the expected limits of a retrospective analysis, we confirm that REG personalized schedules are commonly adopted in everyday clinical practice of high-volume GIST expert centers and correlate with significant improvement of therapeutic outcomes. Based on these results, REG treatment optimization in GIST patients may represent the best strategy to maximize long-term therapy, preserving tolerability and quality of life.