PD-1/PD-L1 inhibitors for locally advanced nasopharyngeal carcinoma: a systematic review and meta-analysis based on randomized controlled trials

The treatment of locally advanced nasopharyngeal carcinoma(LA-NPC) is challenged by recurrence and metastasis(R/M), and even though concurrent chemoradiotherapy(CRT) is the standard regimen, new strategies are urgently needed to improve patient prognosis. In recent years, PD-1/PD-L1 inhibitors, as an important representative of immunotherapy, have shown potential in several studies. However, systematic evidence on the efficacy and safety of PD-1/PD-L1 inhibitors in LA-NPC is insufficient. Therefore, this study aimed to comprehensively assess the efficacy and safety of PD-1/PD-L1 inhibitors in LA-NPC treatment by systematic review and meta-analysis methods. We systematically searched Medline, Embase, and the Cochrane Library (as of March 2025) using subject terms combined with free words to include all randomized controlled trials (RCTs) on PD-1 or PD-L1 inhibitors for LA-NPC. The primary outcome metrics were progression-free survival (PFS), overall survival (OS), event-free survival (EFS), and grade ≥ 3 adverse events (AEs). We conducted a systematic review and meta-analysis of studies that met the inclusion criteria. A total of 2 studies involving 575 participants were included. This meta-analysis showed that patients who received PD-1 inhibitor monotherapy combined with CRT had improved PFS (HR: 0.40, 95% CI: 0.18–0.89) and EFS (HR: 0.59, 95% CI: 0.38–0.92). For distant metastasis rate and locoregional recurrence rate, PD-1 inhibitor monotherapy combined with CRT was more effective, reaching (OR: 0.50,95% CI: 0.30–0.85 I²=0%, P = 0.8) and (OR: 0.43,95% CI: 0.22–0.81 I²=39%, P = 0.2), respectively, which were significantly lower than patients who received only CRT. However, there was no significant difference in OS (HR: 0.83, 95% CI: 0.48–1.43,I²=0%, P = 0.34). Safety analysis showed that PD-1 inhibitor treatment was accompanied by a significantly increased risk of immune-related adverse events(IRAEs)(Peto OR: 11.14, 95% CI: 7.79–15.93 I²=93%, P < 0.0001) and incidence of > = grade 3 AEs (OR: 1.50, 95% CI: 1.04–2.17 I²=0%, P = 0.7). The meta-analysis showed that PD-1 inhibitors combined with CRT in LA-NPC improved their disease control (in terms of PFS and EFS) and reduced disease recurrence and metastasis, but the effect on OS is unknown and increases the risk of IRAEs. The current evidence is based on limited study data, and its exact efficacy and safety need to be confirmed with more high-quality data.