Department of Medical Oncology, Gustave Roussy Cancer Campus, Institut d'Oncologie Thoracique, Gustave Roussy, Université Paris-Saclay, Villejuif, France; Department of Pulmonary Diseases, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.
Department of Medical Oncology, Gustave Roussy Cancer Campus, Institut d'Oncologie Thoracique, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
J Thorac Oncol. 2019 Jul;14(7):1244-1254. doi: 10.1016/j.jtho.2019.02.009. Epub 2019 Feb 16.
Although frequent in NSCLC, patients with brain metastases (BMs) are often excluded from immune checkpoint inhibitor (ICI) trials. We evaluated BM outcome in a less-selected NSCLC cohort.
Data from consecutive patients with advanced ICI-treated NSCLC were collected. Active BMs were defined as new and/or growing lesions without any subsequent local treatment before the start of ICI treatment. Objective response rate (ORR), progression-free survival, and overall survival (OS) were evaluated. Multivariate analyses were performed by using a Cox proportional hazards model and logistic regression.
A total of 1025 patients were included; the median follow-up time from start of ICI treatment was 15.8 months. Of these patients, 255 (24.9%) had BMs (39.2% active, 14.3% symptomatic, and 27.4% being treated with steroids). Disease-specific Graded Prognostic Assessment (ds-GPA) score was known for 94.5% of patients (35.7% with a score of 0-1, 58.5% with a score of 1.5-2.5, and 5.8% with a score of 3). The ORRs with BM versus without BM were similar: 20.6% (with BM) versus 22.7% (without BM) (p = 0.484). The intracranial ORR (active BM with follow-up brain imaging [n = 73]) was 27.3%. The median progression-free survival times were 1.7 (95% confidence interval [CI]: 1.5-2.1) and 2.1 (95% CI: 1.9-2.5) months, respectively (p = 0.009). Of the patients with BMs, 12.7% had a dissociated cranial-extracranial response and two (0.8%) had brain pseudoprogression. Brain progression occurred more in active BM than in stable BM (54.2% versus 30% [p < 0.001]). The median OS times were 8.6 months (95% CI: 6.8-12.0) with BM and 11.4 months (95% CI: 8.6-13.8) months with no BM (p = 0.035). In the BM subgroup multivariate analysis, corticosteroid use (hazard ratio [HR] = 2.37) was associated with poorer OS, whereas stable BMs (HR = 0.62) and higher ds-GPA classification (HR = 0.48-0.52) were associated with improved OS.
In multivariate analysis BMs are not associated with a poorer survival in patients with ICI-treated NSCLC. Stable patients with BM without baseline corticosteroids and a good ds-GPA classification have the best prognosis.
尽管非小细胞肺癌（NSCLC）中脑转移（BMs）很常见，但患者通常被排除在免疫检查点抑制剂（ICI）试验之外。我们评估了一个选择较少的 NSCLC 患者队列中的 BM 结果。
收集了连续接受晚期 ICI 治疗的 NSCLC 患者的数据。有活性的 BM 定义为新的和/或生长的病变，在开始 ICI 治疗前没有任何后续的局部治疗。评估了客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。采用 Cox 比例风险模型和 logistic 回归进行多变量分析。
共纳入 1025 例患者；从开始 ICI 治疗到随访的中位时间为 15.8 个月。其中 255 例（24.9%）有 BM（39.2%有活性，14.3%有症状，27.4%接受了类固醇治疗）。94.5%的患者有疾病特异性分级预后评估（ds-GPA）评分（0-1 分 35.7%，1.5-2.5 分 58.5%，3 分 5.8%）。有 BM 与无 BM 的 ORR 相似：20.6%（有 BM）与 22.7%（无 BM）（p=0.484）。有颅内 ORR（有 BM 并进行了脑影像学随访[n=73]）为 27.3%。无进展生存期中位数分别为 1.7（95%CI：1.5-2.1）和 2.1（95%CI：1.9-2.5）个月（p=0.009）。有 BM 的患者中，12.7%有颅外反应分离，2 例（0.8%）有脑假性进展。有活性 BM 的脑进展发生率高于稳定 BM（54.2%比 30%[p<0.001]）。有 BM 的中位 OS 时间为 8.6 个月（95%CI：6.8-12.0），无 BM 的中位 OS 时间为 11.4 个月（95%CI：8.6-13.8）（p=0.035）。在 BM 亚组的多变量分析中，皮质类固醇的使用（HR=2.37）与较差的 OS 相关，而稳定的 BM（HR=0.62）和较高的 ds-GPA 分类（HR=0.48-0.52）与改善的 OS 相关。
多变量分析显示，BMs 与接受 ICI 治疗的 NSCLC 患者的生存不良无关。无基线皮质类固醇且 ds-GPA 分类良好的稳定 BM 患者预后最佳。
