Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
J Thorac Oncol. 2018 Nov;13(11):1771-1775. doi: 10.1016/j.jtho.2018.06.004. Epub 2018 Jun 20.
Checkpoint inhibitors augment the immune system's natural surveillance mechanisms and have increasing applications in NSCLC. Immunosuppressive corticosteroids are also frequently used in this population to treat unwanted inflammation. In view of this mechanistic opposition, we investigated the interaction between nivolumab and corticosteroids in patients with advanced NSCLC.
A retrospective review of the charts of 210 patients with NSCLC who were treated with nivolumab at the Cleveland Clinic was performed. Use of systemic corticosteroids (equivalent to >10 mg of prednisone/d) during nivolumab therapy was associated with the objective outcomes number of nivolumab cycles and overall survival.
In all, 66 patients (31%) received concurrent systemic corticosteroids during nivolumab therapy. The most common indications included sequelae from active or treated brain metastases (27%) and chronic obstructive pulmonary disease or other respiratory disease (21%). For patients with early exposure to steroids (within the first 30 days of nivolumab therapy) (12% [n=25]), the median number of nivolumab cycles was 2, compared with five cycles in patients who were not exposed to corticosteroids (p = 0.002). The median overall survival time for patients who received steroids during the first 30 days was 4.3 months, compared with 11 months for patients who did not receive steroids (hazard ratio for death = 2.30, 95% confidence interval: CI 1.27-4.16, p = 0.006 in multivariate analysis).
Nearly one-third of patients with NSCLC treated with nivolumab were prescribed concurrent corticosteroids during the course of nivolumab therapy. Patients exposed to corticosteroids during the first cycle of nivolumab received fewer total cycles of nivolumab, suggesting decreased clinical benefit, and they had shorter overall survival.
检查点抑制剂增强了免疫系统的自然监控机制，并在 NSCLC 中得到了越来越多的应用。免疫抑制性皮质类固醇也常用于该人群以治疗不必要的炎症。鉴于这种机制上的对立，我们研究了纳武单抗和皮质类固醇在晚期 NSCLC 患者中的相互作用。
对克利夫兰诊所接受纳武单抗治疗的 210 例 NSCLC 患者的图表进行了回顾性审查。纳武单抗治疗期间使用全身性皮质类固醇（相当于 >10mg 泼尼松/天）与客观结果（纳武单抗周期数和总生存期）有关。
共有 66 例（31%）患者在纳武单抗治疗期间接受了同时使用全身性皮质类固醇。最常见的适应症包括活动或治疗后的脑转移瘤的后遗症（27%）和慢性阻塞性肺疾病或其他呼吸系统疾病（21%）。对于早期接触类固醇（纳武单抗治疗的前 30 天内）的患者（12%[n=25]），纳武单抗周期的中位数为 2 个，而未接触皮质类固醇的患者为 5 个周期（p=0.002）。在接受类固醇治疗的前 30 天内接受类固醇治疗的患者的中位总生存时间为 4.3 个月，而未接受类固醇治疗的患者为 11 个月（死亡风险比=2.30，95%置信区间：1.27-4.16，p=0.006 在多变量分析中）。
接受纳武单抗治疗的 NSCLC 患者中，近三分之一在纳武单抗治疗期间同时开具了皮质类固醇处方。在纳武单抗的第一个周期中接触皮质类固醇的患者接受的纳武单抗总周期数较少，这表明临床获益降低，总生存期较短。
