Abstract B039: A Systematic Review and Meta-Analysis of Randomized Controlled Trials to Evaluate the Efficacy of the Addition of Immune Checkpoint Inhibitors in Patients with Locally Advanced Nasopharyngeal Carcinoma
Authors: Srinivasmurthy Ramaditya , Khalid Taimur , Nanda Rishi K , Jones Daniel T , Aboaid Hazem , Ta Jason , Do Kenny , Nguyen Kevin , Fama Karina B , Aamer Sarah , Myat Yin M , Bigcas Jo-Lawrence , 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), typically utilizing cisplatin and 5-fluorouracil as the most common agents. While this approach has significantly improved 5-year survival rates, the integration of novel immune checkpoint inhibitors (ICIs) into treatment regimens aims to enhance efficacy by targeting specific pathways, such as PD-1/PD-L1 and CTLA-4. This meta-analysis systematically evaluates the efficacy of ICIs when combined with standard NPC treatment in those with locally advanced (LA) NPC. 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 were included. A generic inverse variance method was used to calculate the estimated pooled hazard ratio (HR) for progression-free survival/event-free survival (PFS/EFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q test. Fixed effects models were applied. 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 radiotherapy (standard therapy group) vs standard therapy with the addition of ICI sintilimab in a 1:1 randomization ratio. The phase II trial compared the addition of neoadjuvant ICI toripalimab vs placebo in a 2:1 randomization ratio followed by concurrent chemoradiotherapy followed by adjuvant toripalimab vs placebo. The analysis showed a significantly improved PFS/EFS (2 years in the Phase II trial and 3 years in CONTINUUM trial) in the ICI arm compared to the control arm with a 48% reduction in risk of progression (HR 0.52; 95% CI: 0.35-0.77, P=0.0009). The DMFS and LRFS were both also improved in the ICI group compared to the control group with a risk reduction of events of 49% (HR 0.51; 95% CI: 0.32-0.82, P=0.005) and 57% (HR 0.43; 95% CI: 0.25-0.74, P=0.003). In contrast, OS between the treatment and control arm was not statistically significant, however further maturation of the data is required for definitive conclusions. Conclusion: This study revealed that patients with LA NPC treated with ICIs in addition to chemoradiotherapy demonstrated significant benefits in PFS/EFS, DFMS, and LRFS compared to standard chemoradiotherapy suggesting a promising role for these therapies in treatment regimens to improve outcomes. Although overall survival data was not statistically significant, the data is immature and further maturation of data and studies may yet reveal a significant difference with the addition of ICI.
Citation Format: Ramaditya Srinivasmurthy, Taimur Khalid, Rishi K Nanda, Daniel T Jones, 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 Evaluate the Efficacy of the Addition of Immune Checkpoint Inhibitors in Patients with Locally Advanced Nasopharyngeal Carcinoma [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 B039.