Abstract C056: Risk of Immune-related adverse events with immune checkpoint inhibitors in locally advanced nasopharyngeal carcinoma: A meta-analysis of randomized controlled trials

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 June 1st 2025. 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. A fixed effects model was employed. Results: This meta-analysis included 1,016 patients from two phase III trials (CONTINUUM: n=508; DIPPER: n=278) and one phase II trial (Liu Se et al., 2024: n=230), all evaluating immune checkpoint inhibitors (ICIs) in locoregionally advanced nasopharyngeal carcinoma. In CONTINUUM, patients received induction gemcitabine and cisplatin followed by chemoradiotherapy, with or without sintilimab during induction, concurrent, and adjuvant phases. DIPPER randomized patients post-chemoradiotherapy to adjuvant camrelizumab or observation. The phase II trial assessed neoadjuvant and adjuvant toripalimab vs placebo, with a 2:1 randomization before and after chemoradiotherapy. The incidence of the following irAEs was significantly higher in the ICI arm compared to the control arm: any-grade irAEs 71.15% vs 2.26% (RR 22.92; CI: 13.99–37.57, p<0.00001), high-grade irAEs 7.80% vs 0% (RR 23.62; CI: 4.83–115.49, p<0.0001), grade 1 or 2 hypothyroidism 29.04% vs 9.48% (RR 3.04; CI: 2.24–4.11, p<0.00001), any-grade rash 17.34% vs 0.82% (RR 15.57; CI: 6.55–36.98, p<0.00001), high-grade rash 3.31% vs 0% (RR 13.28; CI: 1.86–94.98, p=0.010), any-grade pruritus 20.27% vs 1.44% (RR 12.29 CI: 5.96–25.34, p<0.00001), and any-grade allergic reaction 2.34% vs 0% (RR 7.66; CI: 1.48–39.71, p=0.02). 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. Early detection 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, Jason Ta, Kenny Do, Riccesha Hattin, Abbas Hussain, Yin M. Myat, Sisi Tian, Jo-Lawrence Bigcas, Kyaw Z. Thein. Risk of Immune-related adverse events with immune checkpoint inhibitors in locally advanced nasopharyngeal carcinoma: A meta-analysis of randomized controlled trials [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C056.