Toll-like Receptor Agonists Are Unlikely to Provide Benefits in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Recurrent and metastatic head and neck cancer has limited treatment options and survival time is measured in months. Toll-like receptor agonists have been shown to improve tumor immune responses in preclinical studies and several clinical trials have now been performed. We performed a meta-analysis of existing clinical trials for recurrent and metastatic head and neck cancer and found there was no treatment benefit of these agents. While they do not appear to cause more adverse events, additional clinical trials may need to focus on new agents or drug combinations. ABSTRACT: Background: Recurrent and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) has poor survival rates. Immunotherapy is the standard of care for R/M HNSCC, but objective responses occur in a minority of patients. Toll-like receptor (TLR) agonists promote antitumor immune responses and have been explored in clinical trials. Methods: A search for clinical trials using TLR agonists in HNSCC was performed under PRISMA guidelines. Data on patient characteristics, safety, and efficacy were collected and analyzed. Results: Three phase 1b trials with 40 patients and three phase 2 trials with 352 patients studying TLR8 and TLR9 agonists in combination with other treatment regimens for HNSCC were included. In phase 2 trials, there was no significant change in the objective response rate (RR = 1.13, CI 0.80–1.60) or association with increased grade 3+ adverse events (RR = 0.91, CI 0.76–1.11) associated with TLR agonist use. Conclusion: TLR agonists do not appear to provide additional clinical benefits or increase adverse events in the treatment of HNSCC. Given these results across multiple clinical trials and drug regimens, it is unlikely that additional trials of TLR agonists will demonstrate clinical benefits in HNSCC.