A Systematic Review and Meta-Analysis of the Efficacy and Safety of Regorafenib in the Treatment of Metastatic Colorectal Cancer

Abstract

Background and objective: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Despite advances in treatment, metastatic colorectal cancer (mCRC) remains a significant challenge due to its heterogeneity and resistance to therapy. Regorafenib, a multikinase inhibitor, can inhibit tumor progression through multiple mechanisms, thereby improving patient prognosis. It has emerged as a potential treatment option for mCRC patients who have progressed on standard therapies. This systematic review and meta-analysis aims to evaluate the efficacy and safety of Regorafenib in this patient population, synthesizing data from clinical trials to provide a comprehensive understanding of its role in mCRC treatment.

Methods: A systematic literature search was conducted via the PubMed, Web of Science (WOS), and Embase databases from January 2012 to December 2024. Studies were included if they were randomized controlled trials (RCTs) or clinical trials that reported outcomes of regorafenib treatment in mCRC patients, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Secondary outcomes included the incidence of serious adverse events (SAEs). OS refers to the length of time from the start of treatment until the death of the patient from any cause, while mortality specifically denotes the number of deaths occurring within the study period. Data were extracted by two independent reviewers using a standardized form. The meta-analysis was performed using RevMan 5.0 statistical software.

Results: A total of 5,082 articles were retrieved, and ultimately, 9 eligible studies involving a total of 2,823 patients were included. All 9 included studies reported OS and PFS. In these mCRC patients, the dose of regorafenib was usually 160 mg daily. The meta results indicated that the OS of patients in the regorafenib group was significantly different [MD = 1.33, 95% CI (0.33, 2.33), P = 0.009]. Eight studies reported the ORR of the disease [OR = 1.13, 95% CI (0.73, 1.76), P = 0.57]. Five studies reported the DCR, and the DCR of patients in the regorafenib group was significantly different from that of patients in the control group [OR = 3.45, 95% CI (2.04, 5.84), P < 0.00001]. The incidence of SAEs (> grade 3) was reported in all 9 included studies [OR = 2.48, 95% CI (1.29, 4.73), P = 0.006].

Conclusion: In this systematic review of prospective trials, regorafenib resulted in improved OS with manageable adverse effects for patients with advanced mCRC. Still, considering the safety, future research should focus on investigating the dose optimization of regorafenib, as well as predictive biomarkers for therapeutic efficacy.

Keywords: Colorectal Cancer; Kinase Inhibitor; Meta-Analysis; Regorafenib.