背景:尽管免疫检查点抑制剂(ICIs)为非小细胞肺癌(NSCLC)带来了生存益处,疾病进展仍在发生,对于这些患者的治疗方案没有达成共识。我们设计了一个网络荟萃分析(NMA)来评估ICIs失败后NSCLC的全身治疗方案。
方法:PubMed,Embase,搜索了WebofScience和CochraneLibrary数据库,然后进行文献筛选,然后进行NMA。我们纳入了所有II期和III期随机对照试验(RCTs)。无进展生存期(PFS)和总生存期(OS)使用风险比(HR)进行评估。客观反应率(ORR)和不良事件(AE)使用比值比(OR)和相对风险(RR)效应大小,分别。应用R软件比较贝叶斯NMA结果。
结果:我们最终纳入了6项研究。1322例患者接受ICI加化疗(ICI+化疗),ICI加抗血管生成单克隆抗体(ICI+抗血管抗体),ICI加酪氨酸激酶抑制剂(ICI+TKI),酪氨酸激酶抑制剂加化疗(TKI+化疗),护理标准(SOC)化疗(化疗)。TKI+化疗与较长的PFS相关,较高的ORR(累积排序曲线下的曲面[SUCRA],99.7%,88.2%),ICI+TKI实现了最长的操作系统(SUCRA,82.7%)。ICI+Antiangio-Ab被授予任何级别的不良事件(AE)的最高安全评级,大于或等于3级的不良事件以及导致停止治疗的任何等级的不良事件(SUCRA,95%,82%,93%)。
结论:对于ICIs失败后的非小细胞肺癌,TKI+化疗与较长的PFS和较高的ORR相关,而ICI+TKI与最长的操作系统相关。在安全方面,ICI+Antiangio-Ab最高。
BACKGROUND: Although immune checkpoint inhibitors (ICIs) have brought survival benefits to non-small cell lung cancer (NSCLC), disease progression still occurs, and there is no consensus on the treatment options for these patients. We designed a network meta-analysis (NMA) to evaluate systemic treatment options for NSCLC after failure of ICIs.
METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were searched, then literature screening was followed by NMA. We included all Phase II and III randomized controlled trials (RCTs). Progression-free survival (PFS) and overall survival (OS) used hazard ratio (HR) for evaluation. Objective response rate (ORR) and adverse events (AEs) used odds ratio (OR) and relative risk (RR) effect sizes, respectively. R software was applied to compare the Bayesian NMA results.
RESULTS: We finally included 6 studies. 1322 patients received ICI plus Chemotherapy (ICI + Chemo), ICI plus Anti-angiogenic monoclonal antibody (ICI + Antiangio-Ab), ICI plus Tyrosine kinase inhibitor (ICI + TKI), Tyrosine kinase inhibitor plus Chemotherapy (TKI + Chemo), Standard of Care (SOC), Chemotherapy (Chemo). TKI + Chemo is associated with longer PFS, higher ORR (surface under cumulative ranking curve [SUCRA], 99.7%, 88.2%), ICI + TKI achieved the longest OS (SUCRA, 82.7%). ICI + Antiangio-Ab was granted the highest safety rating for adverse events (AEs) of any grade, AEs greater than or equal to grade 3 and AEs of any grade leading to discontinuation of treatment (SUCRA, 95%, 82%, 93%).
CONCLUSIONS: For NSCLC after failure of ICIs, TKI + Chemo was associated with longer PFS and higher ORR, while ICI + TKI was associated with the longest OS. In terms of safety, ICI + Antiangio-Ab was the highest.