Guo Haoyan, Miao Longjie, Yu Chengdong
Nanhai Hospital of Traditional Chinese Medicine, Jinan University, No.16, Guicheng South Fifth Road, Foshan, Guangdong, 528200, China; Jinan University, Guangzhou, 510632, China.
Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong, 518104, China; Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
Eur J Pharmacol. 2025 Feb 5;988:177219. doi: 10.1016/j.ejphar.2024.177219. Epub 2024 Dec 21.
The use of targeted drugs and immunotherapy has significantly impacted the treatment of Colorectal Cancer. However, horizontal comparison among various regimens is extremely rare. Therefore, we evaluated the survival efficacy of multiple treatment regimens of targeted therapy and/or immunotherapy with or without chemotherapy in patients with Colorectal Cancer.
A systematic search was conducted in PubMed, EMBASE, and Cochrane databases, covering the period from the establishment of the databases to October 29, 2024. To obtain articles that met the inclusion and exclusion criteria and contained the required data for conducting a network meta-analysis (NMA). The NMA evaluated overall survival (OS) and progression-free survival (PFS).
A total of 90 studies were identified, comprising a sample size of 33,167 subjects. In terms of PFS, compared with simple chemotherapy strategies, most of the other single or combined strategies are significantly effective, among which targeted therapy strategies have more advantages. Encorafenib + Binimetinib + Cetuximab (ENC-BIN-CET) shows significant benefits in all comparisons except when compared with Chemotherapy + Cetuximab + Dalotuzumab (Chemo-CET-DAL), Encorafenib + Cetuximab (ENC-CET), and Panitumumab + Sotorasib (PAN-SOT). The ENC-CET and PAN-SOT targeted strategies also show significant benefits. Pembrolizumab (PEM) monotherapy has advantages over all others except when it is not superior to some targeted strategies. Chemotherapy + Bevacizumab + Atezolizumab is only inferior to some strategies. In terms of OS, the combinations of Chemotherapy + Bevacizumab, ENC-CET, Chemotherapy + Panitumumab, and ENC-BIN-CET are superior to simple chemotherapy regimens. ENC-BIN-CET shows OS benefits in all comparisons except some. ENC-CET significantly improves OS in most cases, and PEM also significantly improves OS in some regimens. In the probability ranking of OS and PFS, ENC-BIN-CET has the best effect, followed by ENC-CET.
In conclusion, pembrolizumab is still effective in prolonging survival. Dual- and triple-drug targeted strategies are the best in terms of OS and PFS, and the combination of targeted immunotherapy and chemotherapy also works. However, not all combinations are beneficial. As targeted drugs play an active role, specific drugs for colorectal cancer regimens should be carefully selected.
靶向药物和免疫疗法的应用对结直肠癌的治疗产生了重大影响。然而，各种治疗方案之间的横向比较极为罕见。因此，我们评估了靶向治疗和/或免疫治疗联合或不联合化疗的多种治疗方案对结直肠癌患者的生存疗效。
在PubMed、EMBASE和Cochrane数据库中进行了系统检索，涵盖从数据库建立至2024年10月29日的时间段。以获取符合纳入和排除标准且包含进行网络荟萃分析（NMA）所需数据的文章。该NMA评估了总生存期（OS）和无进展生存期（PFS）。
共纳入90项研究，样本量为33167名受试者。在PFS方面，与单纯化疗策略相比，大多数其他单一或联合策略均显著有效，其中靶向治疗策略优势更大。恩考芬尼+比美替尼+西妥昔单抗（ENC-BIN-CET）在所有比较中均显示出显著益处，但与化疗+西妥昔单抗+达洛珠单抗（Chemo-CET-DAL）、恩考芬尼+西妥昔单抗（ENC-CET）和帕尼单抗+索托拉西布（PAN-SOT）比较时除外。ENC-CET和PAN-SOT靶向策略也显示出显著益处。帕博利珠单抗（PEM）单药治疗优于所有其他治疗，但不优于某些靶向策略。化疗+贝伐单抗+阿替利珠单抗仅劣于某些策略。在OS方面，化疗+贝伐单抗、ENC-CET、化疗+帕尼单抗和ENC-BIN-CET的联合方案优于单纯化疗方案。ENC-BIN-CET在除某些情况外的所有比较中均显示出OS益处。ENC-CET在大多数情况下显著改善OS，PEM在某些方案中也显著改善OS。在OS和PFS的概率排名中，ENC-BIN-CET效果最佳，其次是ENC-CET。
总之，帕博利珠单抗在延长生存期方面仍然有效。在OS和PFS方面，双药和三药靶向策略最佳，靶向免疫治疗与化疗联合也有效。然而，并非所有联合方案都有益。由于靶向药物发挥着积极作用，应仔细选择结直肠癌治疗方案中的特定药物。
