Durvalumab for the treatment of non-small cell lung cancer
Durvalumab for the treatment of non-small cell lung cancer
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DOI：
10.1080/17476348.2018.1494575
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发表时间：
2018-01-01
影响因子：
3.9
通讯作者：
Planchard, David
中科院分区：
文献类型：
--
作者：
Mezquita, Laura;Planchard, David
简介：在非小细胞肺癌（NSCLC）中，免疫治疗是当今最重要和最具突破性的全身治疗方法之一，主要以抗细胞毒性T淋巴细胞相关蛋白4（CTLA-4）和程序性死亡蛋白1或配体1（PD-1/PD-L1）的抗体为代表。Durvalumab（MEDI 4736）是一种高亲和力的人源IgG 1单克隆抗体，可与PD-1和CD 80结合，阻断PD-L1，但不阻断PD-L2。涵盖的领域：在晚期NSCLC患者中，durvalumab已证明具有活性和可接受的耐受性，特别是在EGFR和ALK野生型人群中PD-L1肿瘤表达率为25%的情况下。然而，初步数据显示，EGFR突变和ALK阳性患者的疗效较低。最近在局部晚期患者中进行的PACIFIC研究的结果将durvalumab作为放化疗后巩固治疗的标准治疗，从而获得了美国食品药品监督管理局（FDA）的批准。专家评论：早期数据表明，durvalumab与CTLA-4抑制剂曲美木单抗（tremelimumab）联合使用具有良好的活性，无论PD-L1表达如何，并且可能与其他药物（如铂双联化疗）联合使用。然而，与联合用药相关的治疗相关毒性是决策过程中获益-风险评价的一个重要方面。正在进行的III期试验的结果将提供启发性数据，以确认durvalumab在NSCLC患者管理中的地位。
Introduction: In non-small cell lung cancer (NSCLC), immunotherapy is one of today's most important and ground-breaking systemic treatments, mainly represented by antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death protein 1 or ligand 1 (PD-1/PD-L1). Durvalumab (MEDI4736) is a high-affinity human IgG1 monoclonal antibody that binds to PD-1 and CD80, blocking PD-L1, but not PD-L2.Areas covered: In advanced NSCLC patients, durvalumab has demonstrated activity and acceptable tolerability, particularly with 25% PD-L1 tumor expression in the EGFR and ALK wild-type population. However, preliminary data have shown lower efficacy in EGFR mutant and ALK-positive patients. The results from the recent PACIFIC study in locally advanced patients have placed durvalumab as standard of care in consolidation after chemoradiation, leading to Food and Drug Administration (FDA) approval.Expert commentary: Early data suggest promising activity for durvalumab with the CTLA-4 inhibitor tremelimumab, regardless of PD-L1 expression, and potentially in combination with other drugs such as platinum-doublet chemotherapy. However, treatment-related toxicity associated with the combinations is an important aspect of the benefit-risk evaluation in the decision-making process. Results of ongoing phase III trials will provide illuminating data to confirm the place of durvalumab in the management of NSCLC patients.