KRASG12C抑制剂在KRASG12C突变晚期实体瘤中的疗效和安全性的单臂Meta分析

Efficacy and Safety of KRASG12C Inhibitors in Advanced Solid Tumors with KRASG12Cmutated:A Single-arm Meta-analysis

目的系统研究KRASG12C抑制剂在KRASG12C突变晚期实体瘤中的疗效和安全性。方法计算机检索PubMed、The Cochrane Library、Web of Science、Embase、CNKI和CBM数据库,收集关于KRASG12C抑制剂在KRASG12C突变晚期实体瘤的临床研究,检索时限为建库至2022年10月12日。由两名研究者独立筛选文献、提取资料并评估纳入研究的偏倚风险,采用RevMan 5.4软件进行Meta分析。结果共纳入4篇文献,均为单臂临床研究。完成临床Ⅰ、Ⅱ期试验的KRASG12C抑制剂有Sotorasib和Adagrasib两种,各两篇文献。共388例患者参与疗效评价,394例患者参与安全性评价。Meta分析结果显示:患者疾病客观缓解率为35%,总体疾病控制率为82%,疾病稳定率为45%。患者严重不良事件发生率为2%,一般不良事件发生率为28%,患者所有不良事件发生率为79%。NSCLC患者疾病部分缓解率为38%。结论KRASG12 C抑制剂Sotorasib和Adagrasib治疗晚期实体瘤表现出良好的疗效和较高的安全性。

Objective To systematically study the efficacy and safety of KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated.Methods Computer searches from PubMed,The Cochrane Library,Web of Science,Embase,CNKI,and CBM databases were conducted to collect clinical studies on KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated,with a search time from inception to October 12,2022.Then,two investigators independently screened the literature,extracted information,assessed the risk of bias in included studies,and performed meta-analyses using RevMan 5.4 software.Results There were four publications included,all of which were single-arm clinical studies.The KRASG12C inhibitors that completed clinical phaseⅠandⅡtrials were sotorasib and adagrasib,with two publications each.A total of 388 and 394 patients were included in the efficacy evaluation and safety evaluation,respectively.Results of the Meta-analysis showed that the patients had objective response rate,overall disease control,and disease stabilization rates of 35%,82%,and 45%,respectively.In addition,the rate of serious adverse events,general adverse events,and all adverse events in patients was 2%,28%,and 79%,respectively.Moreover,the rate of partial remission of disease in NSCLC patients was 38%.Conclusion The KRASG12C inhibitors sotorasib and adagrasib exhibited good efficacy and high safety in advanced solid tumors.