ABSTRACT
BACKGROUND: Immune 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. METHODS: Clinical 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. RESULTS: Twenty 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. CONCLUSIONS: Our 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.