Abstract B042: Assessing the risk of locoregional, general, hematological, and late adverse events in patients with locally advanced nasopharyngeal carcinoma treated with immune checkpoint inhibitors - a systematic review and meta-analysis
Authors: Khalid Taimur , Srinivasmurthy Ramaditya , Nanda Rishi K , Jones Daniel T , Aboaid Hazem , Ta Jason , Do Kenny , Nguyen Kevin , Fama Karina , Aamer Sarah , Myat Yin M , Bigcas Jo-Lawrence M , Thein Kyaw Z 
Published: February 2025

Abstract
Background: Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor of the nasopharyngeal mucosa, with a high prevalence in East and Southeast Asia. The standard treatment for advanced-stage NPC is chemoradiation therapy (CRT), with chemotherapeutic agents typically consisting of cisplatin and 5-fluorouracil. While this approach has significantly improved 5-year survival rates, it is associated with substantial treatment-related adverse effects (AEs). The integration of novel immune checkpoint inhibitors (ICIs) into treatment regimens aims to enhance efficacy and potentially mitigate adverse effects by targeting specific pathways, such as PD-1/PD-L1 and CTLA-4. This meta-analysis evaluates the safety profile of ICIs when combined with standard NPC treatment in those with locally advanced (LA) NPC to provide a clearer understanding of the associated general, locoregional, hematological, and late AEs. Methods: A comprehensive literature search was conducted using MEDLINE and EMBASE databases from inception through November 16th, 2024. Phase II and III randomized controlled trials (RCTs) utilizing ICIs in LA NPC reporting 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 572 patients from a phase III RCT (CONTINUUM: n=423) and a phase II RCT ( n=149) were included in this meta-analysis. The CONTINUUM trial compared chemotherapy induction with gemcitabine and cisplatin followed by cisplatin CRT (standard therapy group) vs standard therapy with the addition of sintilimab in a 1:1 randomization ratio. The phase II trial compared the addition of neoadjuvant toripalimab vs placebo in a 2:1 randomization ratio followed by concurrent chemoradiotherapy followed by adjuvant toripalimab vs placebo. The analysis revealed no statistically significant difference between the ICI and control arms in terms of any or high-grade mucositis, dermatitis, dry mouth, nausea, vomiting, weight loss, anemia, leukopenia, late adverse events, dysphagia, impaired hearing, or grade 1 or 2 peripheral neuropathy. Conclusion: This study revealed that patients with LA NPC treated with ICIs in addition to CRT have a similar safety profile in regards to general, hematological, locoregional, and late adverse events compared to the standard therapy. Given the comparable safety profile to the standard of care, this would support the addition of ICIs to the standard therapeutic regimen of LA NPC.
Citation Format: Taimur Khalid, Ramaditya Srinivasmurthy, Rishi K Nanda, Daniel T Jones, Hazem Aboaid, Jason Ta, Kenny Do, Kevin Nguyen, Karina Fama, Sarah Aamer, Yin M Myat, Jo-Lawrence M Bigcas, Kyaw Z Thein. Assessing the risk of locoregional, general, hematological, and late adverse events in patients with locally advanced nasopharyngeal carcinoma treated with immune checkpoint inhibitors - a systematic review and meta-analysis [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 B042.