The treatment landscape of driver-negative non-small-cell lung cancer (NSCLC) is rapidly evolving. Immune-checkpoint inhibitors, specifically those targeting PD-1 or PD-L1, have demonstrated durable efficacy in a subset of patients with NSCLC, and these agents have become the cornerstone of first-line therapy. Approved immunotherapeutic strategies for treatment-naive patients now include monotherapy, immunotherapy-exclusive regimens or chemotherapy–immunotherapy combinations. Decision making in this space is complex given the absence of head-to-head prospective comparisons, although a thorough analysis of long-term efficacy and safety data from pivotal clinical trials can provide insight into the optimal management of each subset of patients. Indeed, histological subtype and the extent of tumour cell PD-L1 expression are paramount to regimen selection, although other clinicopathological factors and patient preferences might also be relevant in certain scenarios. Finally, several emerging biomarkers and novel therapeutic strategies are currently under investigation, and these might further refine the current treatment paradigm. In this Review, we discuss the current treatment landscape and detail our approach to first-line immunotherapy regimen selection for patients with advanced-stage, driver-negative NSCLC.

驱动阴性非小细胞肺癌 (NSCLC) 的治疗前景正在迅速发展。免疫检查点抑制剂，特别是针对 PD-1 或​​ PD-L1 的抑制剂，已在部分 NSCLC 患者中显示出持久疗效，这些药物已成为一线治疗的基石。现在，已批准的针对初治患者的免疫治疗策略包括单一疗法、免疫疗法独家疗法或化学疗法-免疫疗法组合。由于缺乏头对头的前瞻性比较，这一领域的决策是复杂的，尽管对关键临床试验的长期疗效和安全性数据进行彻底分析可以深入了解每个患者子集的最佳管理。确实，组织学亚型和肿瘤细胞 PD-L1 表达的程度对于方案选择至关重要，尽管在某些情况下其他临床病理因素和患者偏好也可能相关。最后，目前正在研究几种新兴的生物标志物和新的治疗策略，这些可能会进一步完善当前的治疗模式。在这篇综述中，我们讨论了当前的治疗前景，并详细介绍了我们为晚期驱动阴性 NSCLC 患者选择一线免疫治疗方案的方法。