Abstract B044: A Systematic Review and Meta-Analysis of Phase III Randomized Controlled Trials to Assess Risk of Locoregional Adverse Events in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma Treated with Immune Checkpoint Inhibitors
Authors: Nanda Rishi K , Jones Daniel T , Khalid Taimur , Aboaid Hazem , Ta Jason , Srinivasmurthy Ramaditya , Do Kenny , Nguyen Kevin , Fama Karina , Aamer Sarah , Myat Yin M , Bigcas Jo-Lawrence , Thein Kyaw Z 
Published: February 2025

Background: Head and neck squamous cell carcinoma (HNSCC) is a malignancy originating from the mucosal epithelium of the oral cavity, pharynx, and larynx, characterized by aggressive growth, significant morbidity, and high mortality rates worldwide. Traditional treatments like cisplatin, cetuximab, and 5-fluorouracil are effective in achieving tumor control but are often limited by significant toxicities and suboptimal long-term outcomes. Recently, immune checkpoint inhibitors (ICIs), which enhance anti-tumor immunity by targeting the PD-1/PD-L1 pathway, have emerged as promising therapies in HNSCC, offering potential improvements in efficacy and durability of response. This study aims to assess the risk of locoregional adverse events (AEs) in patients with LA HNSCC treated with the combination of immunotherapy and radiation compared to the standard of care. Methods: A comprehensive literature search was conducted using MEDLINE, and EMBASE databases from inception through November 16th, 2024. Phase III randomized controlled trials (RCTs) utilizing ICIs in LA HNSCC reporting locoregional AEs were included. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed using Cochran's Q-statistic. Fixed effects model was employed. Results: A total of 1,674 patients from three Phase III RCTs (KEYNOTE-412: n=796; JAVELIN Head and Neck 100: n=692; NRG-HN004: n=186) were included in this meta-analysis. The KEYNOTE-412 and JAVELIN trials compared ICIs (avelumab or pembrolizumab) plus chemoradiotherapy (CRT) to CRT alone, while NRG-HN004 evaluated radiotherapy with concurrent and adjuvant durvalumab versus cetuximab. The incidence of high-grade odynophagia was higher in the ICI arm compared to the control arm (4.28% vs 2.12%, RR 2.09; 95% CI: 1.20-3.65, P=0.01). No statistically significant difference was noted in the ICI arm compared to the control arm regarding the incidence of other locoregional AEs, including any or high-grade stomatitis, radiation-induced skin injury, dry mouth, dysphagia, ⁠dysgeusia, oropharyngeal pain, tinnitus, or any-grade odynophagia. Conclusions: Our analysis showed that patients with LA HNSCC treated with a combination of radiation and ICIs have a higher risk of high-grade odynophagia compared to the standard of care. However, ICIs showed a similar overall locoregional safety profile compared to standard therapy. This would further support the addition of ICIs to the standard treatment of LA HNSCC.

Citation Format: Rishi K Nanda, Daniel T Jones, Taimur Khalid, Hazem Aboaid, Jason Ta, Ramaditya Srinivasmurthy, Kenny Do, Kevin Nguyen, Karina Fama, Sarah Aamer, Yin M Myat, Jo-Lawrence Bigcas, Kyaw Z Thein. A Systematic Review and Meta-Analysis of Phase III Randomized Controlled Trials to Assess Risk of Locoregional Adverse Events in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma Treated with Immune Checkpoint Inhibitors [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B044.