Liang Bingjun, Tang Ming, Huang Chao, Yang Yidian, He Yue, Liao Shengrong, Shen Weizeng
Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Baoan District), Shenzhen, 518100, China.
Radiotherapy Department, The Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Baoan District), Shenzhen, 518100, China.
J Gastrointest Cancer. 2024 Dec 22;56(1):36. doi: 10.1007/s12029-024-01158-9.
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.
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.
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].
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.
结直肠癌（CRC）是全球癌症相关死亡的主要原因。尽管治疗取得了进展，但转移性结直肠癌（mCRC）因其异质性和对治疗的耐药性，仍然是一个重大挑战。瑞戈非尼是一种多激酶抑制剂，可通过多种机制抑制肿瘤进展，从而改善患者预后。它已成为在标准治疗中进展的mCRC患者的一种潜在治疗选择。本系统评价和荟萃分析旨在评估瑞戈非尼在该患者群体中的疗效和安全性，综合临床试验数据以全面了解其在mCRC治疗中的作用。
通过PubMed、科学网（WOS）和Embase数据库对2012年1月至2024年12月的文献进行系统检索。纳入的研究需为随机对照试验（RCT）或报告mCRC患者瑞戈非尼治疗结果的临床试验，包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和疾病控制率（DCR）。次要结局包括严重不良事件（SAE）的发生率。OS指从治疗开始到患者因任何原因死亡的时间长度，而死亡率具体指研究期间发生的死亡人数。由两名独立 reviewers 使用标准化表格提取数据。使用RevMan 5.0统计软件进行荟萃分析。
共检索到5082篇文章，最终纳入9项符合条件的研究，共2823例患者。所有9项纳入研究均报告了OS和PFS。在这些mCRC患者中，瑞戈非尼的剂量通常为每日160mg。荟萃分析结果表明，瑞戈非尼组患者的OS有显著差异[MD = 1.33，95%CI（0.33，2.33），P = 0.009]。8项研究报告了疾病的ORR[OR = 1.13，95%CI（0.73，1.76），P = 0.57]。5项研究报告了DCR，瑞戈非尼组患者的DCR与对照组患者有显著差异[OR = 3.45，95%CI（2.04，5.84），P < 0.00001]。所有9项纳入研究均报告了SAE（>3级）的发生率[OR = 2.48，95%CI（1.29，4.73），P = 0.006]。
在这项对前瞻性试验的系统评价中，瑞戈非尼改善了晚期mCRC患者的OS，且不良反应可控。不过，考虑到安全性，未来研究应侧重于研究瑞戈非尼的剂量优化以及治疗疗效的预测生物标志物。
