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Review
. 2025 Sep:168:107582.
doi: 10.1016/j.oraloncology.2025.107582. Epub 2025 Aug 9.

The role of systemic therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma progressed to immunotherapy: A systematic review and meta analysis

Affiliations
Review

The role of systemic therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma progressed to immunotherapy: A systematic review and meta analysis

Alicia Tosoni et al. Oral Oncol. 2025 Sep.

Abstract

Introduction: Immunotherapy with or without chemotherapy has become standard first line treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), altering the second-line treatment landscape. After progression to first line no standardized systemic treatments have been identified. Advanced lines of therapy in pre-immune checkpoint inhibitors (ICIs) era led to very modest clinical impact.

Methods: We carried out a systematic review and meta-analysis of the literature assessing observational and interventional trials assessing the impact of advanced lines of treatment in HNSCC previously treated with ICIs. Primary outcome were progression free survival rate at 6 (PFS-6) and 12-months (PFS-12) and Overall Survival rate at 6 (OS-6) and 12-months (OS-12).

Results: We identified 17 relevant studies for a total of 925 patients. In this population a second line therapy led to a PFS-6 and PFS-12 of 47% (95%CI; 37-56%) and 23% (95%CI; 16-33%) respectively. The pooled OS-6 and OS-12 rate were 70% (95%CI; 63-76%) and 41% (95%CI; 35-47%), respectively. All analyses performed presented a significant level of heterogeneity.

Conclusion: Advanced line of systemic treatment in patients progressed to ICIs should be proposed since potentially associate to survival improvement.

Keywords: Chemotherapy; Head and neck cancer; Immunotherapy; Second line.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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