Comparative safety of immune checkpoint inhibitors in recurrent or metastatic head and neck squamous cell carcinoma: a systematic review and network meta-analysis.

BACKGROUND: To indirectly compare the safety of immune checkpoint inhibitors (ICIs) in the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) by network meta-analysis (NMA).

METHODS: Through August 1, 2023, we searched PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov for randomized clinical trials (RCTs) of ICI-based treatment for R/M HNSCC. Outcomes of interest included overall and organ-specific immune-related adverse events (irAEs). Addis 16.5 software was used to perform NMA. Confidence in Network Meta-Analysis (CINeMA) was used to assess confidence in the evidence.

RESULTS: Nine RCTs were included in this NMA, involving a total of 4016 patients. The general safety of ICI-based treatments in descending order was as follows: Durvalumab + Tremelimumab, Camrelizumab + Chemotherapy, Durvalumab, Toripalimab + Chemotherapy, Pembrolizumab, Pembrolizumab + Chemotherapy, Nivolumab, Tremelimumab. There were differences in the toxicity profile among Toripalimab + Chemotherapy (dermatologic irAEs), Camrelizumab + Chemotherapy (hypothyroidism), Nivolumab + Ipilimumab (hyperthyroidism, pneumonitis), Pembrolizumab (nephrotoxicity), Pembrolizumab + Chemotherapy (colitis). ICI-based treatment increased the incidence of endocrine irAEs (hyperthyroidism and hypothyroidism) and pneumonitis compared to conventional therapy. Besides, the combination of dual ICIs resulted in a greater occurrence of irAEs compared to the use of a single ICI.

CONCLUSIONS: The safety ranking of treatments based on ICIs is significantly influenced by specific irAEs. These irAEs, which vary in type and severity, play a crucial role in determining the overall safety profile of each ICI regimen.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023460267.