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免疫检查点抑制剂在非小细胞肺癌治疗中的现状。

Current status of immune checkpoint inhibitors in treatment of non-small cell lung cancer.

机构信息

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Korean J Intern Med. 2019 Jan;34(1):50-59. doi: 10.3904/kjim.2018.179. Epub 2018 Sep 3.

Abstract

Lung cancer remains a leading cause of cancer mortality worldwide, including in Korea. Systemic therapy including platinum-based chemotherapy and targeted therapy should be provided to patients with stage IV non-small cell lung cancer (NSCLC). Applications of targeted therapy, such as an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and anaplastic lymphoma kinase (ALK) inhibitors, in patients with NSCLC and an EGFR mutation or ALK gene rearrangement has enabled dramatic improvements in efficacy and tolerability. Despite advances in research and a better understanding of the molecular pathways of NSCLC, few effective therapeutic options are available for most patients with NSCLC without druggable targets, especially for patients with squamous cell NSCLC. Immune checkpoint inhibitors such as anti-cytotoxic T lymphocyte antigen-4 or anti-programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) have demonstrated durable response rates across a broad range of solid tumors, including NSCLC, which has revolutionized the treatment of solid tumors. Here, we review the current status and future approaches of immune checkpoint inhibitors that are being investigated for NSCLC with a focus on pembrolizumab, nivolumab, atezolizumab, durvalumab, and ipilimumab.

摘要

肺癌仍然是全世界癌症死亡的主要原因,包括在韩国。应向 IV 期非小细胞肺癌(NSCLC)患者提供包括铂类化疗和靶向治疗在内的全身治疗。针对 NSCLC 患者的表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)和间变性淋巴瘤激酶(ALK)抑制剂等靶向治疗的应用,以及 EGFR 突变或 ALK 基因重排,使疗效和耐受性有了显著改善。尽管在研究方面取得了进展,对 NSCLC 的分子途径有了更好的理解,但对于大多数没有可用药靶点的 NSCLC 患者,包括鳞状细胞 NSCLC 患者,很少有有效的治疗选择。免疫检查点抑制剂,如抗细胞毒性 T 淋巴细胞抗原-4 或抗程序性死亡-1(PD-1)或程序性死亡配体 1(PD-L1),在包括 NSCLC 在内的广泛实体瘤中均显示出持久的缓解率,这彻底改变了实体瘤的治疗方法。在这里,我们回顾了正在研究的用于 NSCLC 的免疫检查点抑制剂的现状和未来方法,重点介绍了 pembrolizumab、nivolumab、atezolizumab、durvalumab 和 ipilimumab。

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