Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan.
Expert Rev Anticancer Ther. 2019 Dec;19(12):1009-1016. doi: 10.1080/14737140.2019.1699407. Epub 2019 Dec 3.
: The prognosis of patients with advanced non-small cell lung cancer (NSCLC) remains poor, with a 5-year overall survival rate of around 15%. Immune checkpoint inhibitors, such as programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) inhibitors, have opened a new era in the management of NSCLC. Three checkpoint inhibitors (nivolumab, pembrolizumab, and atezolizumab) are currently approved by the US Food and Drug Administration (FDA) for advanced NSCLC. Durvalumab, an anti-PD-L1 antibody, is under investigation in several trials.: This article reviews the pharmacological properties, clinical efficacy, and safety of durvalumab as monotherapy and in combination with other drugs for the treatment of locally advanced and advanced NSCLC.: Durvalumab as monotherapy or in combination with tremelimumab was effective with well-tolerated safety profiles for advanced NSCLC in several phase I or II studies. The PACIFIC study assessed the effectiveness of durvalumab as maintenance therapy following definitive chemoradiotherapy for unresectable stage III NSCLC, and met its primary endpoints of progression-free survival and overall survival. These results led to FDA approval for this NSCLC population. It will be exciting to follow ongoing phase III studies assessing how durvalumab fits into the rapidly evolving therapeutic landscape for advanced NSCLC.
: 晚期非小细胞肺癌(NSCLC)患者的预后仍然较差,5 年总生存率约为 15%。免疫检查点抑制剂,如程序性细胞死亡蛋白 1 和程序性死亡配体 1(PD-L1)抑制剂,为 NSCLC 的治疗开辟了一个新时代。三种检查点抑制剂(nivolumab、pembrolizumab 和 atezolizumab)目前已被美国食品和药物管理局(FDA)批准用于晚期 NSCLC。抗 PD-L1 抗体 durvalumab 正在多项试验中进行研究。
: 本文综述了 durvalumab 作为单药治疗以及与其他药物联合治疗局部晚期和晚期 NSCLC 的药理学特性、临床疗效和安全性。
: 在几项 I 期或 II 期研究中,durvalumab 单药或与 tremelimumab 联合治疗晚期 NSCLC 具有有效的疗效和良好的安全性。PACIFIC 研究评估了 durvalumab 作为不可切除的 III 期 NSCLC 放化疗后维持治疗的疗效,达到了无进展生存期和总生存期的主要终点。这些结果促使 FDA 批准了这一 NSCLC 人群的适应证。目前正在进行的 III 期研究将评估 durvalumab 在不断发展的晚期 NSCLC 治疗领域中的作用,这将是令人兴奋的。