PD-1/PD-L1 inhibitors plus chemotherapy in cervical cancer: A systematic review and meta-analysis

Objective: This systematic review and meta-analysis aimed to appraise the comparative efficacy and safety of appending programmed death-1 (PD-1) or PD-ligand 1 (PD-L1) checkpoint blockade to standard chemotherapy in cervical cancer, with prespecified analyses across both the full randomized cohort and the PD-L1-enriched subset. Materials and Methods: In accordance with PRISMA 2020 guidelines, a comprehensive electronic search was conducted across PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and ProQuest up to September 2025, targeting phase III randomized trials that incorporated PD-1 or PD-L1 blockade into a chemotherapy backbone. Pooled effect estimates were derived using random-effects modeling, generating hazard ratios (HR) for survival endpoints and risk ratios (RR) for tumor response. Methodological rigor was gauged with the Cochrane Risk of Bias 2 tool, while small-study effects were explored through DOI plots supplemented by the LFK index. Results: Five phase III randomized controlled trials comprising 3,302 patients were included. The addition of PD-1/PD-L1 inhibitors to chemotherapy significantly improved overall survival [HR: 0.66, 95% confidence interval (CI): 0.60-0.73] and progression-free survival (HR: 0.68, 95% CI: 0.60-0.78), with low heterogeneity I2=0%. Objective response rates was modestly increased (RR: 1.14, 95% CI: 1.02-1.26). Survival benefits were mainly driven by PD-1 inhibitors (pembrolizumab and cadonilimab), whereas PD-L1 inhibitors showed less consistent effects. Absolute survival gains within 24 months were modest. Immune-related endocrine events, particularly hyperthyroidism and hypothyroidism, were more frequent, but severe toxicities (grade ≥3) were not significantly increased. Conclusion: PD-1-targeting immunochemotherapy prolongs survival in cervical cancer while maintaining acceptable tolerability, positioning it as a leading treatment option for eligible patients. Further biomarker-driven and head-to-head trials are needed to optimize treatment selection.