Supplementary Material for: Additional immunotherapy to standard of care for unresectable locally advanced head and neck squamous cell carcinoma: a meta-analysis

Background The role of immunotherapy in the treatment of locally advanced head and neck squamous cell carcinoma (LA HNSCC) remains uncertain, particularly in cases of unresectable LA HNSCC. This meta-analysis aimed to evaluate the efficacy of immunotherapy in patients with unresectable LA HNSCC through a systematic review of the existing literature.
Methods This meta-analysis followed a registered protocol on the INPLASY platform with the registration number INPLASY202510102. We systematically collected studies that compared the combination of immunotherapy and standard of care (SOC) with SOC alone for patients with unresectable LA HNSCC. Review Manager, Stata, and R software were employed to conduct single-group rate meta-analysis, pairwise meta-analysis, and Bayesian network meta-analysis.
Results A meta-analysis of fifteen eligible studies involving 3,055 patients revealed no significant improvement in progression-free survival (PFS) or overall survival (OS) with the addition of immunotherapy. Specifically, in patients with human papilloma-positive (HPV+) LA HNSCC, the combination of pembrolizumab and concurrent chemoradiotherapy (CCRT) resulted in 2-year PFS and OS rates of 93% and 97%, respectively. In contrast, LA HNSCC patients treated with chemoradiotherapy followed by sequential pembrolizumab exhibited 2-year PFS and OS rates of 89% and 94%, respectively. Furthermore, our study demonstrated that the combination of pembrolizumab and CCRT achieved a higher 2-year PFS rate compared to the combination of avelumab and CCRT.
Conclusion Although the addition of immunotherapy to SOC regimens did not result in a survival benefit, patients with HPV+ unresectable LA HNSCC may potentially derive benefit from immunotherapy.