Efficacy of two programmed cell death 1 combination regimens in recurrent and/or metastatic head and neck carcinoma: A real-world retrospective study

Background

The combination of programmed cell death 1 (PD-1) inhibitors with molecularly targeted agents, including anti-epidermal growth factor receptor monoclonal antibody (cetuximab) and multi-targeted tyrosine kinase inhibitor (such as anlotinib), has emerged as promising therapeutic strategies in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, comparisons of efficacy between the dual-agent regimens remain unexplored.

Aim

To evaluate the comparative survival benefits and treatment responses of PD-1 inhibitor plus cetuximab vs PD-1 inhibitor plus anlotinib in R/M HNSCC.

Methods

In this real-world study, 24 patients who received PD-1 inhibitors combined with targeted agents at Peking University Cancer Hospital between November 2018 and May 2024 were retrospectively assessed. Patients were stratified into two groups: Anti-PD-1 plus cetuximab (n = 13) and anti-PD-1 plus anlotinib (n = 11). Clinical characteristics and follow-up outcomes were collected, and the overall response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) of the two strategies were analyzed.

Results

The anti-PD-1 plus cetuximab group achieved an ORR of 27.3% and a DCR of 90.9%, while the anti-PD-1 plus anlotinib group showed an ORR of 40.0% and a DCR of 100%. The anti-PD-1 plus cetuximab group demonstrated significantly prolonged OS compared to the anti-PD-1 plus anlotinib group (19.2 months vs 5.8 months; hazard ratios = 0.37; P = 0.036). Survival benefits were consistently observed in subgroups, including patients with programmed death-ligand 1 combined positive score (CPS) ≥ 20 (29.7 months vs 4.1 months; P = 0.013), CPS ≥ 1 (29.7 months vs 4.1 months; P = 0.034), and those receiving first-line treatment (29.7 months vs 4.4 months; P = 0.024). PFS differences were not statistically significant (6.5 months vs 4.4 months, P = 0.448).

Conclusion

Both combination strategies showed antitumor activity in R/M HNSCC. In this retrospective real-world cohort, PD-1 inhibitor plus cetuximab was associated with prolonged OS, whereas PD-1 inhibitor plus anlotinib showed favorable disease control. Larger prospective studies are warranted to confirm these findings.