Efficacy and safety of PD-1/PD-L1 inhibitors versus chemotherapy or cetuximab in the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma: a meta-analysis
In brief
PD-1 blockers reduce death risk 20% and severe toxicity 60% in head-neck cancer
In a pooled analysis of five trials involving 1,700 patients with platinum-refractory recurrent or metastatic head-neck squamous cell carcinoma, PD-1/PD-L1 inhibitors lowered overall mortality by about one-fifth and cut grade 3-5 adverse events by roughly three-quarters compared with chemotherapy or cetuximab. Response rates and progression-free survival were similar, and further trials are needed to confirm these findings.
- Journal
- Frontiers in pharmacology (Q1)
- Published
- 31 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Zhongji Chen, Zhong Zhong, Weiming Liang, Qiwen Feng, Minyao Wu, Lidai Lin, et al.
- PMID
- 42602046
- DOI
- 10.3389/fphar.2026.1675407
Why clinicians should know about it
- Picked for Epidemiology (top studies of the week, 16 August 2026).
Abstract
INTRODUCTION: This meta-analysis was designed to compare the efficacy and safety of PD-1/PD-L1 inhibitors versus chemotherapy or cetuximab in the treatment of platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). MATERIALS AND METHODS: Four databases (PubMed, Embase, Web of Science, and Cochrane Library) were searched for RCTs comparing PD-1/PD-L1 inhibitors versus chemotherapy or cetuximab in the treatment of platinum-refractory R/M HNSCC, from the database's establishment to 2 January 2026. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events (trAEs) were subjected to meta-analyses. RESULTS: Five RCTs were included in the meta-analysis. The meta-analysis included a group of 1,700 patients diagnosed with platinum-refractory R/M HNSCC. Within this cohort, 926 patients were administered PD-1/PD-L1 inhibitors, while 774 patients received chemotherapy or cetuximab. Compared with chemotherapy or cetuximab, PD-1/PD-L1 inhibitors yielded superior OS (HR: 0.80, 95% CI: 0.72 to 0.89, P < 0.01), lower incidence of grade 3-5 trAEs (RR: 0.37, 95% CI: 0.30 to 0.45, P < 0.01) and any grade trAEs (RR = 0.74, 95% CI: 0.69 to 0.79, P < 0.01). There was no statistically significant difference in the ORR (RR: 1.01, 95% CI: 0.71 to 1.51, P = 0.94) or PFS (HR: 1.00, 95% CI: 0.90 to 1.11, P = 0.99) between the two groups. CONCLUSION: The results indicated that PD-1/PD-L1 inhibitors were effective for platinum-refractory R/M HNSCC particularly in populations with high PD-L1 expression and exhibited a superior safety profile compared to chemotherapy or cetuximab. Additional well designed RCTs are required in the future to validate our conclusion. CLINICAL TRIAL REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251020053, identifier PROSPERO (CRD420251020053).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.