Efficacy and safety of immune checkpoint inhibitors for locoregionally advanced, recurrent and metastatic nasopharyngeal carcinoma: a systematic review of phase III randomised controlled trials.

Immune checkpoint inhibitors (ICIs) are an emerging treatment option for cancer. Many randomised controlled trials (RCTs) using ICIs have been conducted on nasopharyngeal carcinoma (NPC) patients, some of which are phase III trials of locoregionally advanced and recurrent/metastatic NPCs. We performed a systematic review to qualitatively assess the efficacy and safety of ICIs in NPC patients. PubMed/MEDLINE, ScienceDirect, Google Scholar, Google, preprint servers, and references were thoroughly searched using Boolean search string (except for references) from inception through April 28, 2025. Full articles and conference abstract that met the eligibility criteria, such as reported studied population, intervention, comparison and outcome, were included. The quality of included studies was assessed with the Cochrane risk of bias (RoB) version 1.0 tool. Meta-analysis was not performed due to data heterogeneity, mainly from methodological variations. Seven phase III trials were shortlisted and tabulated. Three studies described on locoregionally advanced NPC (LANPC), with one article showing moderate RoB and two articles showing high RoB, while three out of four studies on recurrent/metastatic NPC had low RoB. Studies with high RoB provide low certainty/reliability, while those with low RoB offer higher reliability. Each study was unique in ICI usage and study design, including disease stage, adjuvant versus combination therapy, and participant selection criteria. Three high RoB studies, with two studies belonging to LANPC, reported negative effects (p > 0.05) on overall survival (OS). Two low RoB recurrent/metastatic studies reported positive outcome. Progression-free survival (PFS) was met (p < 0.01) in three low RoB recurrent/metastatic NPC studies. PFS [Hazard ratio-HR 0.52 (95% Confidence interval (CI): 0.37-0.73); p < 0.001] and OS [HR 0.63 (95% CI: 0.45-0.89); p < 0.01] were met in 1 low RoB recurrent/metastatic study (toripalimab). Overall, grade ≥ 3 adverse events, including immune-related ones (with rashes being the most common), were manageable. Based on our systematic review, combining ICIs with standard chemotherapy is probably a promising approach for PFS in recurrent/metastasic NPC patients. However, due to high RoB it is inconclusive for LANPC, and high-quality studies are needed.