DOI: 10.37349/etat.2026.1002403 ISSN: 2692-3114

Addition of immune checkpoint inhibitor to standard of care chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma: a systematic review and meta-analysis

Ramaditya Srinivasmurthy, Jason Ta, Sharif Afifi, Taimur Khalid, Hazem Aboaid, Rishi Kumar Nanda, Daniel Thomas Jones, Kenny Do, Kevin Nguyen, Karina Fama, Sarah Aamer, Yin Mon Myat, Jo-Lawrence Bigcas, Kyaw Zin Thein
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Background: Preliminary findings from this study were previously published as a conference abstract (https://doi.org/10.1158/2326-6074.IO2025-B039). Immune checkpoint inhibitors (ICIs) have shown activity in nasopharyngeal carcinoma (NPC), but their efficacy and safety when integrated with standard chemoradiotherapy (CRT) for locally advanced NPC remain under investigation. We performed a systematic review and meta-analysis of randomized controlled trials evaluating the efficacy and safety of integrating ICIs with standard CRT-based treatment in patients with locally advanced NPC. Methods: MEDLINE and EMBASE were searched from inception through September 1, 2025, for English-language phase II or III randomized controlled trials evaluating ICIs plus standard therapy. Eligible studies reported efficacy outcomes, including progression-free/event-free survival (PFS/EFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS), and/or safety outcomes. Hazard ratios (HRs) were pooled using the generic inverse variance method, and risk ratios (RRs) for adverse events were pooled using the Mantel-Haenszel method. Fixed-effect models were used, with heterogeneity assessed using I2 statistics. Results: Three trials randomized 1,022 patients: CONTINUUM (n = 423), DIPPER (n = 450), and a phase II toripalimab trial (n = 149). The pooled safety population included 998 patients. ICIs significantly improved PFS/EFS [HR 0.54; 95% confidence interval (CI): 0.40–0.72; P < 0.0001], DMFS (HR 0.52; 95% CI: 0.36–0.75; P = 0.0005), and LRFS (HR 0.47; 95% CI: 0.31–0.71; P = 0.0003). OS favored the ICI arm but was not statistically significant (HR 0.77; 95% CI: 0.49–1.20; P = 0.24). ICIs increased immune related adverse events, whereas most CRT-associated locoregional and hematologic toxicities were not significantly increased. Discussion: Adding ICIs to standard CRT based therapy significantly improved disease control outcomes, including PFS/EFS, DMFS, and LRFS, without broadly worsening the overall CRT associated toxicity profile. Longer follow up is needed to determine whether these early disease control benefits translate into a statistically significant OS advantage.

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