Efficacy and safety of adding immune checkpoint inhibitors to standard chemotherapy or chemoradiotherapy for advanced or recurrent cervical cancer: a meta-analysis.

Background: Immune checkpoint inhibitors (ICIs) combined with standard chemotherapy (CT) or chemoradiotherapy (CRT) have shown promising results in recent randomized controlled trials (RCTs) for advanced or recurrent cervical cancer (CC). However, comprehensive evidence is needed to evaluate their efficacy and safety, particularly in the context of patient subgroups and immune response mechanisms. This meta-analysis aimed to synthesize data from RCTs and apply trial sequential analysis (TSA) to validate findings. Methods: We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library from database inception through 19 December 2025. RCTs that evaluated the efficacy and safety of ICIs combined with CT or CRT for advanced or recurrent CC were identified and relevant data were extracted. Meta-analyses were performed to pool hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), and risk ratios (RRs) for objective response rate (ORR) and adverse events (AEs). TSA was applied to control the risk of false-positive and false-negative findings for outcomes including PFS, OS, ORR, any grade and grade 3-5 AEs. AEs were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5.0. Results: 5 RCTs totaling 3302 patients with CC met the inclusion criteria. The pooled analysis revealed that compared with CT or CRT (with or without placebo) the addition of ICIs to CT or CRT significantly improved PFS (HR = 0.661, 95% CI: 0.599-0.731; 95% prediction interval [PI]: 0.541-0.811) and OS (HR = 0.664, 95% CI: 0.590-0.747; 95% PI: 0.562-0.785). TSA confirmed the robustness of these findings. While the pooled ORR showed a numerical increase (RR = 1.117, 95% CI: 1.035-1.205), the 95% PI (0.888-1.404) suggested limited robustness. Subgroup analyses showed that the PFS and OS benefits were particularly pronounced in patients with a PD-L1 combined positive score (CPS) ≥ 1, while those with CPS <1 did not derive significant benefit. Safety analyses indicated that adding ICIs did not increase the risk of all-cause AEs of any grade (RR = 1.002, 95% CI: 0.996-1.008; 95% PI: 0.991-1.012), but was associated with a higher incidence of grade 3-5 AEs (RR = 1.076, 95% CI: 1.032-1.123; 95% PI: 1.021-1.144). Conclusion: Adding ICIs to CT or CRT significantly improves survival outcomes in advanced or recurrent CC, particularly in PD-L1-positive patients. However, the increased risk of grade 3-5 AEs underscores the need for vigilant toxicity monitoring and management. These findings highlight the potential of ICIs to enhance immune-mediated tumor control, offering a promising therapeutic option for selected patient populations.