Li Ji, Wang Min, Xu Shuhui, Li Yuying, Li Jiatong, Yu Jinming, Zhu Hui
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Front Pharmacol. 2022 May 17;13:841623. doi: 10.3389/fphar.2022.841623. eCollection 2022.
Brain metastases are more and more common among patients with non-small cell lung cancer (NSCLC). TKI therapy could provide ideal outcomes for patients harboring epidermal growth factor receptor or ALK mutations. For wild-type patients, however, survival is poor because there are few effective treatments other than radiotherapy. Immune checkpoint inhibitors (ICIs) have changed the management of advanced NSCLC. However, the exclusion of patients with active brain metastasis (BM) from most ICI trials precludes the generalization of results. Accordingly, a variety of appropriate real-world studies and clinical trials are being developed to evaluate tumor response. Increasingly encouraging results have suggested that ICIs could be active in the central nervous system (CNS) in select patients with high PD-L1 expression and low CNS disease burden. With the extensive use of ICIs in NSCLC patients with BM, many important questions have emerged concerning issues such as the clinical response to a single ICI, use of ICIs combined with chemotherapy or radiation, the biological mechanism and appropriate sequencing of local and systemic therapy combinations, and safety and toxicity. The present review summarizes the advances in systemic ICIs for the treatment of NSCLC patients with BM, discusses factors associated with efficacy and toxicity, and explores future directions.
脑转移在非小细胞肺癌（NSCLC）患者中越来越常见。酪氨酸激酶抑制剂（TKI）治疗可为携带表皮生长因子受体或间变性淋巴瘤激酶突变的患者提供理想疗效。然而，对于野生型患者，由于除放疗外几乎没有其他有效治疗方法，其生存期较差。免疫检查点抑制剂（ICI）改变了晚期NSCLC的治疗方式。然而，大多数ICI试验将有活动性脑转移（BM）的患者排除在外，这使得试验结果无法推广。因此，正在开展各种适当的真实世界研究和临床试验来评估肿瘤反应。越来越令人鼓舞的结果表明，ICI在部分程序性死亡受体配体1（PD-L1）高表达且中枢神经系统（CNS）疾病负担低的患者的中枢神经系统中可能具有活性。随着ICI在有BM的NSCLC患者中的广泛应用，出现了许多重要问题，如对单一ICI的临床反应、ICI与化疗或放疗联合使用、局部和全身治疗联合的生物学机制及合适顺序，以及安全性和毒性等问题。本综述总结了全身ICI治疗有BM的NSCLC患者的进展，讨论了与疗效和毒性相关的因素，并探索了未来的发展方向。
