Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
Medical Oncology, Parkview Cancer Institute, Fort Wayne, IN, USA.
Cancer Med. 2021 Feb;10(3):923-932. doi: 10.1002/cam4.3675. Epub 2020 Dec 19.
Immunocheckpoint inhibitors (ICIs) have become a standard pharmacological therapy in non-small cell lung cancer (NSCLC). Because brain metastases (BMs) have historically been listed as exclusion criteria in previous clinical trials involving ICIs in advanced NSCLC, the survival benefit from ICI in NSCLC patients with BMs remains unclear. The National Cancer Database was queried for stage IV NSCLC patients with or without BMs between 2014 and 2015. Overall survival (OS) of stage IV NSCLC patients who received immunotherapy and that of stage IV NSCLC patients who did not receive immunotherapy were compared according to the presence or absence of BMs. Multivariable logistic analyses identified the clinical characteristics predictive of overall survival. A propensity score analysis was conducted with the aim of adjusting the potential biases arising from the clinical characteristics. This study included 42,512 patients with stage IV NSCLC; 11,810 patients with BMs and 30,702 patients without BMs. In univariate analysis, stage IV NSCLC patients with BMs treated with immunotherapy had a significantly longer OS than those without immunotherapy after propensity score matching (median OS: 12.8 vs 10.1 months, hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.72-0.89, p < 0.0001). Multivariable Cox modeling after propensity score matching confirmed the survival benefit from ICI for stage IV NSCLC patients with BMs (HR: 0.75, 95% CI: 0.67-0.83, p < 0.0001). The HR in NSCLC patients without BMs treated with ICI compared with those without ICI was 0.77 (95% CI: 0.73-0.82, p < 0.0001). Survival in stage IV NSCLC patients with BMs was significantly improved by ICI treatment at levels comparable to those without BMs using a retrospective database. ICI may be one of the promising treatment options for stage IV NSCLC patients with BMs. These findings should be validated in future prospective studies.
免疫检查点抑制剂(ICIs)已成为非小细胞肺癌(NSCLC)的标准药物治疗方法。由于脑转移(BMs)在以前涉及晚期 NSCLC 中 ICIs 的临床试验中一直被列为排除标准,因此 ICI 对 NSCLC 伴 BMs 患者的生存获益仍不清楚。从 2014 年至 2015 年,国家癌症数据库(National Cancer Database)对有或无 BMs 的 IV 期 NSCLC 患者进行了查询。根据是否存在 BMs,比较了接受免疫治疗的 IV 期 NSCLC 患者和未接受免疫治疗的 IV 期 NSCLC 患者的总生存(OS)。多变量逻辑分析确定了预测总生存的临床特征。进行了倾向评分分析,旨在调整来自临床特征的潜在偏差。本研究纳入了 42512 例 IV 期 NSCLC 患者;其中 11810 例患者存在 BMs,30702 例患者不存在 BMs。在单变量分析中,在进行倾向评分匹配后,接受免疫治疗的有 BMs 的 IV 期 NSCLC 患者的 OS 明显长于未接受免疫治疗的患者(中位 OS:12.8 个月比 10.1 个月,风险比 [HR]:0.80,95%置信区间 [CI]:0.72-0.89,p<0.0001)。进行倾向评分匹配后的多变量 Cox 模型证实,有 BMs 的 IV 期 NSCLC 患者接受 ICI 治疗具有生存获益(HR:0.75,95%CI:0.67-0.83,p<0.0001)。与未接受 ICI 治疗的患者相比,接受 ICI 治疗的无 BMs 的 NSCLC 患者的 HR 为 0.77(95%CI:0.73-0.82,p<0.0001)。使用回顾性数据库,有 BMs 的 IV 期 NSCLC 患者接受 ICI 治疗可显著改善生存。ICI 可能是 BMs 的 IV 期 NSCLC 患者的一种有前途的治疗选择之一。这些发现应在未来的前瞻性研究中得到验证。