Tang Li-Bo, Peng Ying-Long, Chen Ji, Li Jia-Ting, Zheng Mei-Mei, Wu Lv, Lu Chang, Wei Xue-Wu, Cai Dong-Xuan, Guo Zhi, Ren Zi-Rui, Lv Si-Di, Deng Yu, Chen Zhi-Hong, Xu Chong-Rui, Zhou Qing
School of Medicine, South China University of Technology, Guangzhou, China.
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Nat Rev Clin Oncol. 2025 Jun 9. doi: 10.1038/s41571-025-01029-7.
Lung cancer remains the leading cause of cancer-related mortality globally, with many patients diagnosed with advanced-stage disease. Treatment in this setting relies on systemic therapies, including chemotherapy, targeted therapy and immunotherapy. Immune-checkpoint inhibitors (ICIs), which promote or restore antitumour immunity by inhibiting immunosuppressive signalling pathways, are currently the most widely used immunotherapies in these patients. However, immune-related adverse events (irAEs) or disease progression often necessitate discontinuation of these agents, leaving many patients with limited subsequent treatment options. In this scenario, ICI rechallenge has emerged as a potential strategy. Despite this potential, evidence for ICI rechallenge after either disease progression or irAEs in patients with non-small-cell lung cancer is limited and evidence for those with small cell lung cancer seems to be non-existent. In this Review, we provide a comprehensive overview of the available data on ICI rechallenge in the context of both disease progression and irAEs, including a summary of current guidance on clinical management and detailed discussions of safety and efficacy. We also highlight important unanswered questions in an attempt to guide future research in this area.
肺癌仍然是全球癌症相关死亡的主要原因，许多患者被诊断为晚期疾病。在这种情况下，治疗依赖于全身治疗，包括化疗、靶向治疗和免疫治疗。免疫检查点抑制剂（ICIs）通过抑制免疫抑制信号通路来促进或恢复抗肿瘤免疫力，目前是这些患者中使用最广泛的免疫疗法。然而，免疫相关不良事件（irAEs）或疾病进展往往需要停用这些药物，导致许多患者后续治疗选择有限。在这种情况下，ICI再挑战已成为一种潜在策略。尽管有这种潜力，但非小细胞肺癌患者在疾病进展或出现irAEs后进行ICI再挑战的证据有限，而小细胞肺癌患者的相关证据似乎不存在。在本综述中，我们全面概述了在疾病进展和irAEs背景下ICI再挑战的现有数据，包括当前临床管理指南的总结以及对安全性和有效性的详细讨论。我们还强调了重要的未解决问题，试图为该领域的未来研究提供指导。
