文章：

非小细胞肺癌在疾病进展或复发后再次应用免疫检查点抑制剂的疗效评估

Efficacy of NSCLC Rechallenge with Immune Checkpoint Inhibitors following Disease Progression or Relapse

原文发布日期：18 March 2024

DOI: 10.3390/cancers16061196

类型: Article

开放获取: 是

英文摘要：

Immune checkpoint inhibitors (ICIs) are at the forefront of advanced non-small-cell lung cancer (NSCLC) treatment. Still, only 27–46% of patients respond to initial therapy with ICIs, and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6–3.1 months and a Disease Control Rate (DCR) of 21.4–41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75–81%, according to post hoc analyses of several clinical trials. Future research on ICI rechallenge for NSCLC should focus on better patient stratification to reflect the underlying biology of immunotherapy resistance more accurately. In this review, we summarize evidence regarding rechallenge immunotherapy efficacy following NSCLC disease progression or relapse, as well as ongoing trials on immunotherapy rechallenge.

摘要翻译： 

免疫检查点抑制剂（ICIs）是晚期非小细胞肺癌（NSCLC）治疗的前沿手段。然而，仅有27%至46%的患者对初始ICIs治疗产生应答，且其中高达65%的患者在四年内产生耐药性。疾病进展（PD）后，治疗选择有限，二线或三线化疗的客观缓解率（ORR）仅为10%。在此背景下，ICIs再挑战成为NSCLC治疗中一个颇具吸引力的选择。 目前关于ICIs再挑战疗效的数据大多基于小规模、经过多线治疗且异质性患者群体的回顾性真实世界研究。尽管存在这些局限性，这些研究表明，在未经选择的、因疾病进展而停止初始ICIs治疗的NSCLC患者群体中，ICIs单药再挑战通常效果不佳，中位无进展生存期（PFS）为1.6至3.1个月，疾病控制率（DCR）为21.4%至41.6%。然而，存在一个亚群能从该策略中获益，进一步明确该亚群的特征至关重要。 此外，根据多项临床试验的事后分析，对于在完成初始免疫治疗方案后停药、并经历一段无免疫治疗间隔期后出现疾病进展的患者，免疫治疗再挑战显示出有前景的疗效，其疾病控制率可达75%至81%。未来关于NSCLC的ICIs再挑战研究应侧重于更好的患者分层，以更准确地反映免疫治疗耐药的潜在生物学机制。 本综述总结了关于NSCLC疾病进展或复发后免疫治疗再挑战疗效的证据，以及正在进行的免疫治疗再挑战相关临床试验。

原文链接：

Efficacy of NSCLC Rechallenge with Immune Checkpoint Inhibitors following Disease Progression or Relapse