Xie Xiaoyu, Zhang Jianwei, Hu Huabin, Cai Yue, Wu Zehua, Ling Jiayu, Li Weiwei, Deng Yanhong
Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
Adv Ther. 2020 Oct;37(10):4233-4248. doi: 10.1007/s12325-020-01447-2. Epub 2020 Aug 8.
Although various therapies are available for the treatment of metastatic colorectal cancer (mCRC), there is lack of head-to-head evidence. Recent studies have demonstrated the efficacy of chemotherapy in combination with different biological agents including regorafenib in second-line therapy in patients with mCRC. We conducted a network meta-analysis (NMA) to estimate the relative efficacy and safety of regorafenib in combination with chemotherapy compared to other biological agents with chemotherapy combinations.
A literature search was conducted in PubMed, Embase, and Cochrane databases to identify all randomized controlled trials (RCTs) evaluating the efficacy and safety of bevacizumab, regorafenib, panitumumab, cetuximab, ramucirumab, conatumumab, ganitumab, and aflibercept in combination with chemotherapy against chemotherapy alone as second-line setting from inception to 7 February 2019 in patients with mCRC. The survival outcomes were analyzed by the frequentist statistical approach (R software, netmeta package) while the level of individual treatment arms was assessed using the Bayesian method (R software, gemtc package).
We identified 12 articles involving eight RCTs studies analyzing 6805 patients. The studies compared bevacizumab (3), regorafenib (1), panitumumab (2), cetuximab (3), ramucirumab (1), conatumumab (1), ganitumab (1), and aflibercept (1) against chemotherapy alone as comparator. The progression-free survival (PFS) revealed that regorafenib performed better than aflibercept (HR 0.9631, 95% CI 0.6785-1.367), ganitumab (HR 0.7228, 95% CI 0.3985-1.3109), panitumumab (HR 0.9653, 95% CI 0.6781-1.3742), and ramucirumab (HR 0.9206, 95% CI 0.6504-1.303). Regorafenib performed better than bevacizumab (OR 0.797, 95% CI 0.328-1.88) in terms of tumor response. Safety analysis showed that regorafenib performed better in reducing grade ≥ 3 adverse events (AE) than cetuximab and conatumumab, neutropenia than conatumumab, and fatigue than cetuximab.
Regorafenib combined with chemotherapy might be a potential alternative to conventional therapeutic options in second-line treatment of patients with metastatic colorectal cancer and could be considered as the best option for treating patients with KRAS and BRAF mutated mCRC. However future RCTs are needed to confirm these results.
尽管有多种疗法可用于治疗转移性结直肠癌（mCRC），但缺乏直接对比的证据。最近的研究已证明化疗联合不同生物制剂（包括瑞戈非尼）用于mCRC患者二线治疗的疗效。我们进行了一项网状Meta分析（NMA），以评估瑞戈非尼联合化疗相对于其他化疗联合生物制剂的相对疗效和安全性。
在PubMed、Embase和Cochrane数据库中进行文献检索，以识别所有评估贝伐单抗、瑞戈非尼、帕尼单抗、西妥昔单抗、雷莫西尤单抗、考那单抗、甘尼单抗和阿柏西普联合化疗与单纯化疗作为二线治疗对mCRC患者疗效和安全性的随机对照试验（RCT），检索时间从开始至2019年2月7日。生存结局采用频率统计方法（R软件，netmeta包）分析，而各治疗组水平采用贝叶斯方法（R软件，gemtc包）评估。
我们确定了12篇文章，涉及8项RCT研究，分析了6805例患者。这些研究将贝伐单抗（3项）、瑞戈非尼（1项）、帕尼单抗（2项）、西妥昔单抗（3项）、雷莫西尤单抗（1项）、考那单抗（1项）、甘尼单抗（1项）和阿柏西普（1项）与单纯化疗作为对照进行比较。无进展生存期（PFS）显示，瑞戈非尼的表现优于阿柏西普（HR 0.9631，95%CI 0.6785 - 1.367）、甘尼单抗（HR 0.7228，95%CI 0.3985 - 1.3109）、帕尼单抗（HR 0.9653，95%CI 0.6781 - 1.3742）和雷莫西尤单抗（HR 0.9206，95%CI 0.6504 - 1.303）。在肿瘤反应方面，瑞戈非尼优于贝伐单抗（OR 0.797，95%CI 0.328 - 1.88）。安全性分析表明，瑞戈非尼在减少≥3级不良事件（AE）方面比西妥昔单抗和考那单抗表现更好，在减少中性粒细胞减少方面比考那单抗表现更好，在减少疲劳方面比西妥昔单抗表现更好。
瑞戈非尼联合化疗可能是转移性结直肠癌患者二线治疗中传统治疗方案的潜在替代方案，可被视为治疗KRAS和BRAF突变的mCRC患者的最佳选择。然而，需要未来的RCT来证实这些结果。
