Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
Eur J Cancer. 2017 Aug;81:9-16. doi: 10.1016/j.ejca.2017.05.004. Epub 2017 Jun 3.
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.
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.
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).
Everolimus-induced pneumonitis is associated with improved outcome in patients with mRCC and may serve as a biomarker of everolimus efficacy.
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。
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。
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）。
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。
