Gartrell Benjamin A, Ying Jian, Sivendran Shanthi, Boucher Kenneth M, Choueiri Toni K, Sonpavde Guru, Oh William K, Agarwal Neeraj, Galsky Matthew D
Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA,
Target Oncol. 2014 Sep;9(3):195-204. doi: 10.1007/s11523-013-0289-2. Epub 2013 Jul 13.
Mammalian target of rapamycin (mTOR) inhibitors have gained regulatory approval for use in several cancer types. Pulmonary adverse events associated with mTOR inhibitors are well recognized but their frequency has varied considerably among trials. PubMed and ASCO abstracts were searched to identify clinical trials of mTOR inhibitors in solid tumors. Twenty-two eligible trials on which 4,242 patients were treated met the criteria for inclusion in this systematic review and meta-analysis. Adverse event data were extracted and used to determine the incidence rate and incidence rate ratio for pneumonitis, dyspnea, and cough. The incidence rate of any grade pneumonitis in patients with solid tumors treated with mTOR inhibitors was 0.11 (95% confidence interval (CI), 0.06-0.17) per patient, while the incidence of grade 3-4 pneumonitis was 0.03 (95% CI, 0.01-0.04) per patient. The incidence rate ratio (IRR) of any grade pneumonitis with mTOR inhibitors relative to controls was 19.0 (95% CI, 6.5-55.4), and for grade 3-4 pneumonitis was 8.0 (95% CI, 2.6-24.1). The incidence rate for any grade and grade 3-4 cough was 0.23 (95% CI, 0.20-0.27) per patient and 0.01 (95% CI, 0.00-0.01) per patient, respectively. The incidence rate for any grade and grade 3-4 dyspnea was 0.15 (95% CI, 0.10-0.21) per patient and 0.03 (95% CI, 0.02-0.04) per patient, respectively. Compared to control, treatment with mTOR inhibitors were associated with a significant increase in any grade cough [IRR = 1.9 (95% CI, 1.6-2.4)] and grade 3-4 dyspnea [IRR = 2.0 (95% CI, 1.2-3.3)]. This study provides an estimation of the risk of pulmonary adverse events in solid tumor patients treated with mTOR inhibitors. While pulmonary adverse events are relatively common with mTOR inhibitors, most are low grade and asymptomatic.
雷帕霉素哺乳动物靶点（mTOR）抑制剂已获得监管部门批准用于多种癌症类型。与mTOR抑制剂相关的肺部不良事件已广为人知，但在各试验中其发生率差异很大。通过检索PubMed和美国临床肿瘤学会（ASCO）摘要，以确定mTOR抑制剂在实体瘤中的临床试验。22项符合条件的试验共纳入4242例接受治疗的患者，符合本系统评价和荟萃分析的纳入标准。提取不良事件数据，用于确定肺炎、呼吸困难和咳嗽的发生率及发生率比。接受mTOR抑制剂治疗的实体瘤患者中，任何级别的肺炎发生率为每位患者0.11（95%置信区间（CI），0.06 - 0.17），而3 - 4级肺炎的发生率为每位患者0.03（95%CI，0.01 - 0.04）。mTOR抑制剂治疗组与对照组相比，任何级别的肺炎发生率比（IRR）为19.0（95%CI，6.5 - 55.4），3 - 4级肺炎的发生率比为8.0（95%CI，2.6 - 24.1）。任何级别的咳嗽发生率为每位患者0.23（95%CI，0.20 - 0.27），3 - 4级咳嗽发生率为每位患者0.01（95%CI，0.00 - 0.01）。任何级别的呼吸困难发生率为每位患者0.15（95%CI，0.10 - 0.21），3 - 4级呼吸困难发生率为每位患者0.03（95%CI，0.02 - 0.04）。与对照组相比，mTOR抑制剂治疗与任何级别的咳嗽[IRR = 1.9（95%CI，1.6 - 2.4）]和3 - 4级呼吸困难[IRR = 2.0（95%CI，1.2 - 3.3）]的显著增加相关。本研究对接受mTOR抑制剂治疗的实体瘤患者肺部不良事件风险进行了评估。虽然mTOR抑制剂相关的肺部不良事件相对常见，但大多数为低级别且无症状。
