A Systematic Review and Network Meta‐Analysis of Regorafenib and TAS‐102 in Refractory Metastatic Colorectal Cancer

Background Regorafenib at different dosing strategies and TAS‐102 are treatment options for refractory metastatic colorectal cancer (mCRC). We aimed to evaluate the comparative effectiveness evidence supporting these different strategies. Materials and Methods We searched different databases for randomized controlled trials evaluating TAS‐102 or regorafenib in patients with refractory mCRC who failed prior oxaliplatin, irinotecan, and fluoropyrimidine. Outcomes of interest included overall survival (OS) and progression‐free survival (PFS). The overall effect was pooled using the DerSimonian random effects model. We conducted network meta‐analysis based on White's multivariate meta‐regression to pool evidence from direct and indirect comparisons. Results Six trials at low risk of bias (2,445 patients) were included. Direct comparisons showed that Rego 160 and TAS‐102 as monotherapy were superior to best‐supportive care (BSC) in terms of PFS (Rego 160: hazard ratio [HR], 0.4; 95% confidence ratio [CI], 0.26–0.63; TAS‐102: HR, 0.46 CI, 0.40–0.52) and OS (Rego 160: HR, 0.67; CI, 0.48–0.93; TAS‐102: HR, 0.67; CI, 0.57–0.80). Network analysis showed no statistically difference in PFS or OS between Rego 160 and TAS‐102. Rego 80+ was superior to BSC in terms of OS (HR, 0.44; CI, 0.23–0.84) and PFS (HR, 0.37; CI, 0.21–0.66). Rego 80+ was associated with statistically nonsignificant improvement in OS and PFS compared with TAS‐102 and Rego 160. Conclusion Regorafenib 160 and TAS‐102 appear to have similar efficacy. Rego 80+ is shown to be superior to BSC. A trend for improved OS was observed with Rego 80+ versus Rego 160 or TAS 102. Implications for Practice Regorafenib at a dose of 160 mg and TAS‐102 appear to have similar efficacy in patients with refractory metastatic colorectal cancer. Regorafenib with a dose escalation strategy is superior to best‐supportive care. Given its tolerability and the observed trend in survival benefit compared with regorafenib 160, dose escalation strategy of regorafenib (80+) may be the preferred option in this setting. 摘要 背景。不同剂量方案的瑞戈非尼和 TAS‐102 是治疗难治性转移性结直肠癌 (mCRC) 的常见治疗方案。我们旨在对支持这些不同治疗方案的有效性比较证据进行评估。 材料和方法。我们在不同数据库中搜索了评估难治性mCRC患者改用 TAS‐102 或瑞戈非尼是否有效的随机对照试验，这些患者既往用奥沙利铂、伊立替康及氟尿嘧啶治疗失败。所关注的预后包括总生存期 (OS) 和无进展生存期 (PFS)。同时，采用 DerSimonian 随机效应模型对总体效应进行了汇总。我们基于 White 多元荟萃回归模型开展了网络荟萃分析，以便从直接和间接对比中收集证据。 结果。包括六项偏倚风险较低的试验(2 445 名患者)。通过直接对比表明，在PFS方面，瑞戈非尼(剂量为 160 mg，Rego 160)和 TAS‐102 要优于最佳支持疗法 (BSC) [Rego 160:风险比 (HR)，0.4；95% 置信比 (CI)，0.26–0.63