Lung cancer remains the most frequent cause of cancer-related mortality.¹ In the last decade, significant advances have been made in the management of metastatic non–small-cell lung cancer (NSCLC), ranging from stratification into multiple therapeutically relevant genomic subsets (eg, EGFR and ALK)^2,3 to the expanding role of immune checkpoint inhibitors.⁴ Currently, three immune checkpoint inhibitors have gained FDA approval for treatment of advanced NSCLC: nivolumab, pembrolizumab, and atezolizumab.^5-7 Although these indications were based on positive phase III trials demonstrating significant overall survival (OS) benefit when compared with docetaxel chemotherapy in the second- and third-line settings, they differ in their programmed death-ligand 1 (PDL1) patient–selection strategy. Although PDL1 status was evaluated in all three trials and was consistently shown to enrich for patients who have a higher likelihood of benefit, label indications for nivolumab and atezolizumab do not stipulate the need for selection on the basis of PDL1 status, whereas use of pembrolizumab is restricted to patients with a tumor proportion score (TPS) ≥ 1%. There has since been continued enthusiasm in targeting the programmed death protein 1/PDL1 axis, with the initiation of several phase II and III trials using a range of patient-enrichment and combinatorial strategies; such trials are poised to define a new therapeutic bar in treatment-naïve NSCLC.

中文翻译：

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通过预先编程的死亡蛋白1 /编程的死亡配体1封锁改变非小细胞肺癌的自然史

肺癌仍然是与癌症相关的死亡率的最常见原因。¹在过去的十年中，转移性非小细胞肺癌（NSCLC）的管理取得了重大进展，从分层到治疗上相关的多个基因组亚类（例如EGFR和ALK）^2,3到不断扩大的作用免疫检查点抑制剂。⁴目前，三种免疫检查点抑制剂已获得FDA批准用于治疗晚期NSCLC：nivolumab，pembrolizumab和atezolizumab。^5-7尽管这些适应症是基于III期临床试验的阳性结果，表明在二线和三线治疗中与多西他赛化疗相比具有显着的总体生存（OS）获益，但它们在编程的死亡配体1（PDL1）患者选择策略上有所不同。尽管在所有三项试验中均评估了PDL1的状态，并且始终显示PDL1的状态可以使受益可能性更高的患者受益，但nivolumab和atezolizumab的标签适应症并未规定需要根据PDL1的状态进行选择，而使用pembrolizumab则是仅限于肿瘤比例评分（TPS）≥1％的患者。此后，人们一直对靶向编程的死亡蛋白1 / PDL1轴充满热情，使用多种患者强化和组合策略启动了多个II期和III期试验；这样的试验准备在未接受过治疗的非小细胞肺癌中定义一个新的治疗标准。