依维莫司相关性肺炎与转移性肾细胞癌患者的良好预后相关。
Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma.
机构信息
Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
出版信息
Eur J Cancer. 2017 Aug;81:9-16. doi: 10.1016/j.ejca.2017.05.004. Epub 2017 Jun 3.
BACKGROUND
Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients.
PATIENTS AND METHODS
Eighty-five mRCC patients received everolimus at Helsinki University Hospital (cohort A). Computed tomography (CT) verified pneumonitis was correlated with outcome using Kaplan-Meier, Cox regression and logistic regression. An independent cohort of 148 everolimus treated mRCC patients (cohort B) at Aarhus University Hospital was assessed for validation.
RESULTS
In cohort A, CT-verified pneumonitis (N = 29, 34.1%) was associated with improved overall survival (OS) (24.7 versus 8.5 months; P < 0.001), progression-free survival (PFS) (5.5 versus 3.2 months; P = 0.002) and clinical benefit rate (CBR) 57.1% versus 24.1% (P = 0.003). In multivariate analyses pneumonitis was associated with improved OS (hazard ratio [HR], 0.22; 95% confidence interval [CI] 0.12-0.44; P < 0.001), PFS (HR 0.37; 95% CI 0.21-0.66; P = 0.001) and CBR (odds ratio [OR] 4.11; 95% CI 1.42-11.95; P = 0.01). In cohort B, CT-verified pneumonitis (N = 29, 19.6%) was associated with improved OS (12.9 versus 6.0 months; P = 0.02), PFS (6.0 versus 2.8 months; P = 0.02) and CBR (79.3% versus 39.5%; P < 0.001). In multivariate analyses pneumonitis was associated with improved OS (HR 0.58; 95% CI 0.36-0.94; P = 0.03), PFS (HR 0.61; 95% CI 0.39-0.95; P = 0.03) and CBR (OR 5.65; 95% CI 2.10-15.18; P = 0.001). In a combined multivariate analysis (N = 233), with pneumonitis as a time-dependent covariate, CT-verified pneumonitis was associated with longer OS (HR, 0.67; 95% CI 0.46-0.97; P = 0.03). Furthermore, in a landmark analysis, pneumonitis was associated with longer OS (17.4 versus 7.8 months; P = 0.01).
CONCLUSIONS
Everolimus-induced pneumonitis is associated with improved outcome in patients with mRCC and may serve as a biomarker of everolimus efficacy.
背景
哺乳动物雷帕霉素靶蛋白抑制剂可能会引起肺炎。我们分析了 everolimus 治疗转移性肾细胞癌（mRCC）患者的肺炎与结局的相关性。
方法
85 例 mRCC 患者在赫尔辛基大学医院接受 everolimus 治疗（队列 A）。使用 Kaplan-Meier、Cox 回归和 logistic 回归分析经计算机断层扫描（CT）证实的肺炎与结局的相关性。在奥胡斯大学医院对 148 例接受 everolimus 治疗的 mRCC 患者（队列 B）进行了独立评估以验证。
结果
在队列 A 中，经 CT 证实的肺炎（N=29，34.1%）与总生存（OS）（24.7 个月与 8.5 个月；P<0.001）、无进展生存（PFS）（5.5 个月与 3.2 个月；P=0.002）和临床获益率（CBR）57.1%与 24.1%（P=0.003）相关。在多变量分析中，肺炎与 OS 改善相关（风险比 [HR]，0.22；95%置信区间 [CI]，0.12-0.44；P<0.001）、PFS（HR 0.37；95%CI 0.21-0.66；P=0.001）和 CBR（比值比 [OR] 4.11；95%CI 1.42-11.95；P=0.01）。在队列 B 中，经 CT 证实的肺炎（N=29，19.6%）与 OS（12.9 个月与 6.0 个月；P=0.02）、PFS（6.0 个月与 2.8 个月；P=0.02）和 CBR（79.3%与 39.5%；P<0.001）改善相关。在多变量分析中，肺炎与 OS 改善相关（HR 0.58；95%CI 0.36-0.94；P=0.03）、PFS（HR 0.61；95%CI 0.39-0.95；P=0.03）和 CBR（OR 5.65；95%CI 2.10-15.18；P=0.001）。在一项联合多变量分析（N=233）中，将肺炎作为时间依赖性协变量，经 CT 证实的肺炎与 OS 延长相关（HR，0.67；95%CI 0.46-0.97；P=0.03）。此外，在一个里程碑分析中，肺炎与 OS 延长相关（17.4 个月与 7.8 个月；P=0.01）。
结论
everolimus 诱导的肺炎与 mRCC 患者的结局改善相关，可能是 everolimus 疗效的生物标志物。
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