Cumulative Dose of Regorafenib in Patients With Metastatic Colorectal Cancer: A Multicenter Cohort Study

Purpose: This study aimed to evaluate the prognostic effect of the cumulative dose (CD) of regorafenib on survival in patients with metastatic colorectal cancer (mCRC). Materials and Methods: This retrospective study utilized the Taipei Medical University Clinical Research Database for analysis. Patients aged ≥ 20 years with mCRC who were prescribed regorafenib between January 2014 and December 2021 were identified and then divided into low- and high-CD groups (≤ 4200 mg vs. > 4200 mg). Overall survival (OS), time-to-treatment discontinuation (TTD), and the incidence of five common adverse events were compared between groups. In addition, natural cubic splines were employed to examine the non-linear relationship between cumulative doses and survival in the multivariate Cox regression model. Results: A total of 259 patients were enrolled, with 130 in the low-CD group and 129 in the high-CD group; the median OS was 4.6 months and 9.8 months, respectively (p < 0.01). The median TTD was 51.5 days for the low-CD group and 72.0 days for the high-CD group (p < 0.01). No significant difference in drug-related adverse events was observed between groups. In the multivariate Cox analysis, a CD ≤ 4200 mg was a negative prognostic factor (hazard ratio 1.41 [95% confidence interval 1.08–1.84], p = 0.01). In addition, patients on a dose range between 4368 and 5376 mg exhibited minimal mortality risk. Conclusion: The cumulative doses of regorafenib > 4200 mg were associated with improved survival. The suggested optimal dose range serves as a reference for dose modification in clinical practice.