Treatment of metastatic non-small-cell lung cancers (NSCLCs) has long been based on cytotoxic chemotherapy. Immune checkpoint inhibitors (ICIs), notably monoclonal antibodies directed against programmed cell death protein-1 (PD-1) or its ligand (PD-L1), have transformed therapeutic standards in thoracic oncology. These ICIs are now the reference first-line therapy, and numerous phase III trials have established their efficacy in treatment-naïve patients. First-line pembrolizumab monotherapy was validated for patients with ≥ 50% of tumor cells expressing PD-L1 and, in the USA, for patients with ≥ 1% PD-L1 positivity. More recently, cemiplimab as monotherapy was also validated for patients whose tumors expressed ≥ 50% PD-L1. Several ICIs (pembrolizumab, atezolizumab, nivolumab, and recently durvalumab) in combination with chemotherapy achieved overall survival gains among “all comers”, compared with chemotherapy alone. The results were more contrasting for paired immunotherapies combining anti-PD-L1 and anti-cytotoxic T-lymphocyte antigen-4 agents, with the benefit/risk balance not yet fully established. Recently, nivolumab–ipilimumab and two chemotherapy cycles limited patient exposure to chemotherapy and obtained positive results compared with the latter alone. However, those phase III trials included selected patients in good general condition and without active brain metastases. Little is known about immunotherapy and combination immunotherapy–chemotherapy efficacies in never-smokers or patients with tumors harboring an epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation. In this review, we report our analysis of the main results available on first-line ICI use, as monotherapy or combined or in combination with chemotherapy, to treat metastatic NSCLCs in general and also for specific populations: the elderly, never-smokers, patients with brain metastases, and those with an EGFR mutation or ALK translocation.

转移性非小细胞肺癌 (NSCLC) 的治疗长期以来一直基于细胞毒性化疗。免疫检查点抑制剂 (ICI)，特别是针对程序性细胞死亡蛋白 1 (PD-1) 或其配体 (PD-L1) 的单克隆抗体，已经改变了胸部肿瘤学的治疗标准。这些 ICI 现在是一线治疗的参考，许多 III 期试验已经确定了它们在初治患者中的疗效。一线 pembrolizumab 单药治疗已针对 ≥ 50% 的肿瘤细胞表达 PD-L1 的患者进行了验证，在美国，针对 ≥ 1% PD-L1 阳性的患者进行了验证。最近，cemiplimab 作为单一疗法也被验证用于肿瘤表达 ≥ 50% PD-L1 的患者。几种 ICI（pembrolizumab、atezolizumab、nivolumab、和最近的 durvalumab）与化疗相结合，与单独化疗相比，在“所有参与者”中实现了总生存期的提高。对于结合了抗 PD-L1 和抗细胞毒性 T 淋巴细胞抗原 4 药物的配对免疫疗法，结果对比更为明显，收益/风险平衡尚未完全确定。最近，nivolumab-ipilimumab 和两个化疗周期限制了患者接受化疗，并且与单独使用后者相比取得了积极的结果。然而，这些 III 期试验包括一般情况良好且没有活动性脑转移的选定患者。关于免疫疗法和联合免疫疗法-化疗对从不吸烟者或携带表皮生长因子受体的肿瘤患者的疗效知之甚少（与单独化疗相比。对于结合了抗 PD-L1 和抗细胞毒性 T 淋巴细胞抗原 4 药物的配对免疫疗法，结果对比更为明显，收益/风险平衡尚未完全确定。最近，nivolumab-ipilimumab 和两个化疗周期限制了患者接受化疗，并且与单独使用后者相比取得了积极的结果。然而，这些 III 期试验包括一般情况良好且没有活动性脑转移的选定患者。关于免疫疗法和联合免疫疗法-化疗对从不吸烟者或携带表皮生长因子受体的肿瘤患者的疗效知之甚少（与单独化疗相比。对于结合了抗 PD-L1 和抗细胞毒性 T 淋巴细胞抗原 4 药物的配对免疫疗法，结果对比更为明显，收益/风险平衡尚未完全确定。最近，nivolumab-ipilimumab 和两个化疗周期限制了患者接受化疗，并且与单独使用后者相比取得了积极的结果。然而，这些 III 期试验包括一般情况良好且没有活动性脑转移的选定患者。关于免疫疗法和联合免疫疗法-化疗对从不吸烟者或携带表皮生长因子受体的肿瘤患者的疗效知之甚少（收益/风险平衡尚未完全建立。最近，nivolumab-ipilimumab 和两个化疗周期限制了患者接受化疗，并且与单独使用后者相比取得了积极的结果。然而，这些 III 期试验包括一般情况良好且没有活动性脑转移的选定患者。关于免疫疗法和联合免疫疗法-化疗对从不吸烟者或携带表皮生长因子受体的肿瘤患者的疗效知之甚少（收益/风险平衡尚未完全建立。最近，nivolumab-ipilimumab 和两个化疗周期限制了患者接受化疗，并且与单独使用后者相比取得了积极的结果。然而，这些 III 期试验包括一般情况良好且没有活动性脑转移的选定患者。关于免疫疗法和联合免疫疗法-化疗对从不吸烟者或携带表皮生长因子受体的肿瘤患者的疗效知之甚少（EGFR ) 突变或间变性淋巴瘤激酶 ( ALK ) 易位。在这篇综述中，我们报告了我们对一线 ICI 使用的主要结果的分析，作为单一疗法或联合疗法或与化学疗法联合治疗，以治疗一般转移性 NSCLC 以及特定人群：老年人、从不吸烟者、患者有脑转移，以及有EGFR突变或ALK易位的患者。