Pabani A, Butts C A
Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB.
Curr Oncol. 2018 Jun;25(Suppl 1):S94-S102. doi: 10.3747/co.25.3750. Epub 2018 Jun 13.
For patients with advanced non-small-cell lung cancer (nsclc) lacking a targetable molecular driver, the mainstay of treatment has been cytotoxic chemotherapy. The survival benefit of chemotherapy in this setting is modest and comes with the potential for significant toxicity. The introduction of immunotherapeutic agents targeting the programmed cell death 1 protein (PD-1) and the programmed cell death ligand 1 (PD-L1) has drastically changed the treatment paradigms for these patients. Three agents-atezolizumab, nivolumab, and pembrolizumab-have been shown to be superior to chemotherapy in the second-line setting. For patients with tumours strongly expressing PD-L1, pembrolizumab has been associated with improved outcomes in the first-line setting. Demonstration of the significant benefits of immunotherapy in nsclc has focused attention on new questions. Combination checkpoint regimens, with acceptable toxicity and potentially enhanced efficacy, have been developed, as have combinations of immunotherapy with chemotherapy. In this review, we focus on the published trials that have changed the treatment landscape in advanced nsclc and on the ongoing clinical trials that offer hope to further improve outcomes for patients with advanced nsclc.
对于缺乏可靶向分子驱动因素的晚期非小细胞肺癌(NSCLC)患者,治疗的主要手段一直是细胞毒性化疗。在这种情况下,化疗的生存获益有限,且存在显著毒性的风险。靶向程序性细胞死亡蛋白1(PD-1)和程序性细胞死亡配体1(PD-L1)的免疫治疗药物的引入,彻底改变了这些患者的治疗模式。三种药物——阿特珠单抗、纳武单抗和帕博利珠单抗——已被证明在二线治疗中优于化疗。对于肿瘤强烈表达PD-L1的患者,帕博利珠单抗在一线治疗中与更好的疗效相关。免疫疗法在NSCLC中的显著益处引发了人们对新问题的关注。已开发出毒性可接受且疗效可能增强的联合检查点方案,以及免疫疗法与化疗的联合方案。在本综述中,我们重点关注已改变晚期NSCLC治疗格局的已发表试验,以及为进一步改善晚期NSCLC患者预后带来希望的正在进行的临床试验。