知识与财富的链接
摘 要：KEYNOTE-177研究是首个探索PD-1抑制剂（帕博利珠单抗）对比传统化疗一线治疗微卫星高度不稳定或错配修复缺陷（MSI-H/dMMR）转移性结直肠癌对总生存期（OS）及无进展生存期（PFS）影响的Ⅲ期随机对照研究。研究设计上,PFS和OS作为双主要研究终点,采用优效性设计,α控制在单侧0.025,其中PFS和OS初始α各分配50%比例。研究结果上,帕博利珠单抗组对比化疗组的OS没有达到显著性差异,但帕博利珠单抗组呈现出了PFS、客观缓解率及安全性方面的优势。尽管OS未达到其统计学预设终点,现有的数据仍支持帕博利珠单抗作为MSI-H/dMMR转移性结直肠癌患者的有效一线治疗方案。
Abstract： The KEYNOTE-177 study is the first randomized, phase 3, controlled study to explore the effects of first-line treatment with PD-1 inhibitors(pembrolizumab) on the overall survival(OS) and progression-free survival(PFS) in microsatellite instability-high/mismatch repair deficient(MSI-H/dMMR) metastatic colorectal cancer versus conventional chemotherapy. For the study design, PFS and OS were used as the co-primary endpoints. Adopting superiority design, one-sided α was controlled at 0.025, and initial α was equally allocated for PFS and OS by 50% respectively. In terms of research results, treatment with pembrolizumab versus chemotherapy did not result in a significant difference on OS, but pembrolizumab group showed improved PFS, objective response rate and safety. Although its statistically prespecified endpoint of OS was not reached, the available data supports pembrolizumab as an effective first-line therapy in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer.
