PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis.
PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis.
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PD-1抑制剂以剂量无关的方式增加癌症患者肺炎的发病率和风险：一项荟萃分析
DOI：
10.1038/srep44173
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发表时间：
2017-03-08
影响因子：
4.6
通讯作者：
Miao J
中科院分区：
文献类型：
--
作者：
Wu J;Hong D;Zhang X;Lu X;Miao J
靶向PD-1的治疗在各种肿瘤类型的患者中显示出显著的持久临床反应率。然而，与PD-1阻滞相关的肺毒性（主要表现为肺炎）的程度和知识仍然不清楚。本研究汇总了来自16项II/III期临床试验的6360例受试者进行荟萃分析，以评价癌症患者中PD-1相关肺炎的总体发生率和风险。抗PD-1免疫治疗期间所有级别的肺炎发生率为2.92%（95%CI：2.18-3.90%），高度级别的肺炎发生率为1.53%（95%CI：1.15-2.04%）。与常规化疗相比，PD-1抑制剂与肺炎风险显著增加相关。此外，在使用PD-1抑制剂治疗的肿瘤类型中，黑色素瘤患者的肺炎发生率最低，而非小细胞肺癌（NSCLC）和肾细胞癌（RCC）患者的肺炎发生率最高。此外，在PD-1抑制剂高剂量组和低剂量组之间，未检测到全级别和高级别肺炎的发生率存在显著差异。总之，与常规化疗药物相比，PD-1抑制剂可能以剂量非依赖性方式与肺炎风险增加相关。不同肿瘤类型患者治疗介导性肺炎的发生率和严重程度差异很大。
Therapies that targeted PD-1 have shown remarkable rates of durable clinical responses in patients with various tumor types. However, the extent and knowledge of pulmonary toxicities associated with PD-1 blockade, mainly manifested as pneumonitis, remains obscure. In this study, a total of 6360 subjects from 16 phase II/III clinical trials were pooled for meta-analysis to evaluate the overall incidence and risk of PD-1 inhibitors-related pneumonitis in cancer patients. The incidence of pneumonitis during anti-PD-1 immunotherapy was 2.92% (95%CI: 2.18–3.90%) for all-grade and 1.53% (95%CI: 1.15–2.04%) for high-grade pneumonitis. Compared with routine chemotherapy, PD-1 inhibitors were associated with a significant increased risk of pneumonitis. Moreover, among the types of tumor treated with PD-1 inhibitors, the melanoma patients have the lowest incidence of pneumonitis, while the non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) patients have the highest. Furthermore, no significant differences were detected in the incidences of all- and high-grade pneumonitis between high-dose and low-dose groups of PD-1 inhibitors. In conclusion, PD-1 inhibitors were probably associated with an increased risk of pneumonitis in a dose-independent manner, compared with routine chemotherapeutic agents. The frequency and severity of treatment-mediated pneumonitis was quite different in patients with various tumor types.