Policlinico S. Orsola-Malpighi, Bologna, Italy.
Policlinico S. Orsola - Malpighi, Via Albertoni 15, 40138 Bologna (BO), Italy.
Ther Adv Respir Dis. 2017 Sep;11(9):353-373. doi: 10.1177/1753465817725486. Epub 2017 Aug 17.
Immune checkpoint inhibitors (ICPIs) are considered one of the most important breakthroughs in cancer treatment of the past decade; notably, different studies of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have reported impressive clinical activity and durable responses in patients with advanced non-small cell lung cancer (NSCLC). These findings have led to the changing of the current therapeutic algorithm of advanced NSCLC, adding a new standard first-line treatment option for patients with PD-L1-positive tumors. Pembrolizumab, a highly selective anti-PD-1 humanized monoclonal antibody, was approved by the United States Food and Drug Administration (US FDA) in October 2016 for previously untreated metastatic NSCLC patients whose tumors have high PD-L1 expression, tumor proportion score (TPS) ⩾ 50%, as well as for metastatic NSCLC patients whose tumors express PD-L1 with TPS ⩾ 1% progressing on or after platinum-based chemotherapy. However, many issues remain outstanding, mainly regarding the identification of an optimal biomarker which can help selecting patients more likely to respond to ICPIs. In this review, we discuss the clinical results obtained so far with the anti-PD-1 pembrolizumab in advanced NSCLC, commenting on the role of PD-L1 as a predictive factor and providing an update of the future perspectives.
免疫检查点抑制剂(ICPI)被认为是过去十年癌症治疗中最重要的突破之一;值得注意的是,不同的程序性死亡蛋白 1(PD-1)和程序性死亡配体 1(PD-L1)抑制剂研究报告称,晚期非小细胞肺癌(NSCLC)患者具有令人印象深刻的临床活性和持久反应。这些发现导致了晚期 NSCLC 当前治疗算法的改变,为 PD-L1 阳性肿瘤患者增加了一种新的标准一线治疗选择。派姆单抗是一种高度选择性的抗 PD-1 人源化单克隆抗体,于 2016 年 10 月获得美国食品和药物管理局(US FDA)批准,用于治疗未经治疗的转移性 NSCLC 患者,这些患者的肿瘤具有高 PD-L1 表达、肿瘤比例评分(TPS) ⩾50%,以及在铂类化疗后进展的肿瘤表达 PD-L1,TPS ⩾1%的转移性 NSCLC 患者。然而,仍有许多悬而未决的问题,主要是关于确定最佳生物标志物,以帮助选择更有可能对 ICPIs 有反应的患者。在这篇综述中,我们讨论了迄今为止使用抗 PD-1 派姆单抗在晚期 NSCLC 中获得的临床结果,评论了 PD-L1 作为预测因子的作用,并提供了未来展望的最新信息。