Regorafenib monotherapy as the later-line treatment for elderly patients with metastatic colorectal cancer: a multicenter real-world study.

Background: Colorectal cancer is one of the tumors with the highest morbidity and mortality rates in China and the world. Regorafenib is a targeted drug for standard third-line treatment of metastatic colorectal cancer (mCRC). Regorafenib monotherapy has shown certain efficacy in the elderly population, but more robust evidence is needed. The aim of this study was to evaluate the dosing characteristics, prognosis, and safety of regorafenib monotherapy in elderly Chinese patients with mCRC. Methods: This retrospective study comprised elderly patients (aged ≥60 years) with mCRC who received regorafenib monotherapy as a third-line or above treatment in 10 hospitals from August 2017 to June 2020. We analyzed the association between different dosing regimens and prognosis. The primary endpoint was overall survival (OS), and other endpoints included progression-free survival (PFS) and adverse events (AEs). Results: In total, 203 patients were included in the analysis. The median PFS was 3.88 months [95% confidence interval (CI): 3.48-5.65], and the median OS was 10.1 months (95% CI: 8.94-12.1). There was no significant difference in the survival curves between the different dosage groups. The multivariate Cox analysis showed a significant benefit in OS in the high final daily dose group (120-160 mg/day) [hazard ratio (HR): 0.45, 95% CI: 0.25-0.84, P=0.01], which was further confirmed by the propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis. No significant association was found between the initial daily dose and prognosis. Nor was any significant association found between PFS and drug dosage. Subsequently, an age subgroup analysis was conducted using 70 years as the cut-off value. In those aged <70 years, the application of higher final doses (120-160 mg/day) was significantly associated with the prolongation of OS compared to a final dose of 80 mg/day [HR (95% CI): 0.38 (0.16-0.91), P=0.03], and the prolongation of OS was predominantly observed in the 120 mg/day dose group [HR (95% CI): 0.24 (0.09-0.67), P=0.006]. Besides, we observed a statistically insignificant increase in the incidence of AEs in the higher dose group compared to the lower dose group. Conclusions: Regorafenib monotherapy was shown to be efficacious in the elderly population, but further evidence is needed for guidance. Based on our multicenter real-world investigation, the final daily dose was significantly associated with OS. For those aged <70 years, maintaining the final dose at 120 mg/day may have prognostic advantages. The suggested medication protocol requires validation through comprehensive clinical trials.