BackgroundImmune checkpoint inhibitors (ICIs) are widely used in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC); however, the toxicity profiles are inconclusive.MethodsClinical trials evaluating ICIs for R/M HNSCC were searched from online databases. The characteristics of the studies and the results of incidences of any grade treatment‐related adverse events (trAEs), grade three or more trAEs, treatment‐related deaths, trAEs leading to discontinuation of treatment, and specific trAEs were extracted.ResultsTwenty studies with 3756 patients were included. The pooled incidences of any grade trAEs, grade three or more trAEs, treatment‐related deaths, trAEs leading to discontinuation of treatment for overall population were 62.07% (95% CI, 59.07%–65.02%), 13.82% (95% CI, 11.23%–16.62%), 0.39% (95% CI, 0.15%–0.71%), 3.99% (95% CI, 2.36%–5.95%), respectively. Programmed cell death protein 1 (PD‐1) inhibitors monotherapy and ICIs combination therapy had significantly higher incidences of any grade trAEs (odds ratio [OR], 1.25, 95% CI, 1.05–1.49 and 1.36, 95% CI, 1.15–1.60, respectively), grade three or more trAEs (OR, 1.41, 95% CI, 1.08–1.84 and 1.79, 95% CI, 1.39–2.30, respectively), trAEs leading to discontinuation of treatment (OR, 3.98, 95% CI, 2.06–7.70 and 10.14, 95% CI, 5.49–18.70, respectively) compared with programmed death‐ligand 1 (PD‐L1) inhibitors monotherapy. ICIs combination therapy had a significantly higher incidence of grade three or more trAEs compared with PD‐1 inhibitors monotherapy (OR, 1.27, 95% CI, 1.03–1.55); however, the incidences of any grade trAEs and trAEs leading to discontinuation of treatment were not significant different.ConclusionsOur study suggests that the incidences of grade three or more trAEs, treatment‐related deaths, and trAEs leading to discontinuation of treatment are low in R/M HNSCC patients treated with ICIs. PD‐L1 inhibitors monotherapy may be safer compared with PD‐1 inhibitors monotherapy and ICIs combination therapy.

中文翻译：

---

免疫检查点抑制剂对复发性或转移性头颈鳞状细胞癌的毒性特征：系统评价和荟萃分析

研究背景免疫检查点抑制剂（ICIs）广泛应用于复发或转移性头颈鳞状细胞癌（R/M HNSCC）；然而，毒性特征尚无定论。方法从在线数据库中检索评估 ICI 治疗 R/M HNSCC 的临床试验。研究特征以及任意级别治疗相关不良事件 (trAE)、三级或以上 trAE、治疗相关死亡、导致治疗停止的 trAE 以及特定 trAE 的发生率结果被提取。 结果 20 项研究，涉及 3756 名患者患者也被包括在内。总体人群中任何级别 trAE、三级或以上 trAE、治疗相关死亡、导致停止治疗的 trAE 的汇总发生率分别为 62.07%（95% CI，59.07%–65.02%）、13.82%（95% CI，分别为 11.23%–16.62%)、0.39% (95% CI, 0.15%–0.71%)、3.99% (95% CI, 2.36%–5.95%)。程序性细胞死亡蛋白 1 (PD-1) 抑制剂单药治疗和 ICI 联合治疗的任何级别 trAE 发生率均显着较高（优势比 [OR]，1.25，95% CI，1.05–1.49 和 1.36，95% CI，1.15–1.60）三级或以上 trAE（分别为 OR，1.41，95% CI，1.08-1.84 和 1.79，95% CI，1.39-2.30），导致停止治疗的 trAE（OR，3.98，95% CI，与程序性死亡配体 1 (PD-L1) 抑制剂单一疗法相比，分别为 2.06–7.70 和 10.14，95% CI，5.49–18.70。与 PD-1 抑制剂单药治疗相比，ICIs 联合治疗的三级或以上 trAE 发生率显着更高（OR，1.27，95% CI，1.03-1.55）；然而，任何级别的 trAE 和导致停止治疗的 trAE 的发生率没有显着差异。结论我们的研究表明，在 R/ 患者中，三级或以上 trAE、治疗相关死亡和导致停止治疗的 trAE 的发生率较低。接受 ICI 治疗的 M HNSCC 患者。与 PD-1 抑制剂单药治疗和 ICI 联合治疗相比，PD-L1 抑制剂单药治疗可能更安全。