2860 - Efficacy and Safety of Immunotherapy vs. Cetuximab Concurrent with Radiotherapy in Cisplatin-Ineligible Locally Advanced Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
Presenter(s)
T. Tun1, T. Khalid2, H. Aboaid3, D. T. Jones4, R. K. Nanda4, Z. T. Win5, S. Afifi4, R. Srinivasmurthy4, J. Ta4, J. L. Bigcas6, and K. Z. Thein7; 1PrimeWest Consortium- Department of Internal Medicine, Shasta Regional Medical Center, Redding, CA, 2Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, 3Department of Internal Medicine, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, 4Touro University Nevada College of Osteopathic Medicine, Las Vegas, NV, 5Department of Internal Medicine, University of California, Riverside, CA, 6Department of Otolaryngology-Head & Neck Surgery, Kirk Kerkorian School of Medicine at UNLV, Las Vegas, NV, 7Division of Hematology and Medical Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV
Purpose/Objective(s): Concurrent radiotherapy (RT) with cisplatin is the standard of care for locally advanced head and neck squamous cell carcinoma (LA HNSCC), but many patients are ineligible due to comorbidities, age, or functional status. While cetuximab has been utilized as the radiosensitizer in cisplatin-ineligible LA HNSCC, recent trials have explored immune checkpoint inhibitors (ICIs) as alternatives. This study aims to evaluate the efficacy and safety of ICIs versus cetuximab concurrent with radiotherapy in cisplatin-ineligible LA HNSCC.
Materials/Methods: A comprehensive literature search of MEDLINE and EMBASE databases was conducted through February 9, 2025. Phase II/III randomized controlled trials (RCTs) utilizing ICIs in cisplatin-ineligible patients with LA HNSCC were included. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) with 95% confidence interval (CI) for survival endpoints, and Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% CI. Heterogeneity was assessed with Cochran’s Q-statistic. Fixed effects model was applied.
Results: A total of 311 patients from one phase II RCT (PembroRad) and one phase II/III RCT (NRG-HN004) were analyzed. Both trials evaluated progression-free survival (PFS), overall survival (OS), as well as safety outcomes. No statistically significant difference was noted between the ICIs + RT and cetuximab + RT groups in terms of 2-year PFS or OS. In terms of safety outcomes, the following events were observed less frequently in the ICIs arm compared to the control arm: any-grade radiation dermatitis (RD) 70.81% vs 81.75% (RR 0.88; 95% CI: 0.77-1.00; p=0.05), high-grade RD 10.27% vs 36.51% (RR 0.35; 95% CI: 0.22-0.55; p<0.00001), and high-grade mucositis 18.38% vs 38.89% (RR 0.56; 95% CI: 0.39-0.80; p=0.002). Incidence of any-grade dry mouth was higher in the ICIs group compared to the control group 65.95% vs 51.59% (RR 1.23; 95% CI: 1.01-1.49; p=0.04). Incidence of all other adverse events, including high-grade dry mouth, any-grade mucositis, any or high-grade dysgeusia, oropharyngeal pain, esophagitis, fatigue, weight loss, and nausea, was not different between the two treatment arms.
Conclusion: This meta-analysis demonstrates that immunotherapy concurrent with radiotherapy has no survival benefit over cetuximab plus radiation in cisplatin-ineligible patients with LA HNSCC. However, immunoradiotherapy was associated with lower rates of radiation dermatitis and high-grade mucositis but higher incidence of any-grade dry mouth, and the safety profile was similar between the two treatment groups otherwise. Further research is needed to refine treatment strategies and identify subgroups that may benefit from immunotherapy.