Abstract B043: A Systematic Review and Meta-Analysis of Randomized Controlled Trials to Assess the Risk of Immune-Related Adverse Effects (irAEs) in Patients with Locally Advanced Nasopharyngeal Carcinoma Treated with Immune Checkpoint Inhibitors

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 locally advanced (LA) NPC is chemoradiation therapy (CRT), with regimens typically consisting of cisplatin and 5-fluorouracil or gemcitabine. The integration of immune checkpoint inhibitors (ICIs) into treatment regimens has shown improved survival benefits, however, it raises concerns for treatment-related adverse events (AEs). This study aims to evaluate the risk of immune-related AEs (irAEs) in patients with LA NPC treated with ICIs. Methods: A comprehensive literature search was conducted using MEDLINE and EMBASE databases from inception through November 16th 2024. Randomized controlled trials (RCTs) utilizing ICIs in LA NPC reporting irAEs 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 incidence of the following irAEs was significantly higher in the ICI arm compared to the control arm: any-grade irAEs 57.47% vs 4.17% (RR 10.71; CI: 6.43–17.85, P<0.00001), high-grade irAEs 10.39% vs 0% (RR 25.82; CI: 3.85–173.38, P=0.0008), grade 1 or 2 hypothyroidism 27.60% vs 2.65% (RR 7.89; CI: 4.11–15.16, P<0.00001), any-grade rash 25% vs 1.14% (RR 16.13; CI: 6.20–41.95, P<0.00001), high-grade rash 5.52% vs 0% (RR 13.28; CI: 1.86–94.98, P=0.010), any-grade pruritus 25% vs 0.76% (RR 22.18; CI: 7.04–69.85, P<0.00001), and any-grade allergic reaction 3.25% vs 0% (RR 2.19; CI: 1.21–61.03, P=0.03). In contrast, the incidence of high-grade pruritus and allergic reaction was not statistically significantly different between the two treatment groups. Conclusion: This study revealed that patients with LA NPC treated with ICIs in addition to CRT have a higher risk of developing irAEs in general compared to those treated with standard therapy. Earlydetection of these AEs and providing the appropriate supportive care is essential to optimize the outcomes and maintain patients’ quality of life and compliance. Citation Format: Ramaditya Srinivasmurthy, Rishi K Nanda, Daniel T Jones, Taimur Khalid, Hazem Aboaid, Jason Ta, Kenny Do, Kevin Nguyen, Karina B Fama, Sarah Aamer, Yin M Myat, Jo-Lawrence Bigcas, Kyaw Z Thein. A Systematic Review and Meta-Analysis of Randomized Controlled Trials to Assess the Risk of Immune-Related Adverse Effects (irAEs) in Patients with Locally Advanced Nasopharyngeal 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 B043.