Meta-analysis shows immune checkpoint inhibitor combinations improve survival and response rates in advanced cervical cancer patients with manageable safety profiles

BackgroundCombination therapy based on immune checkpoint inhibitors (ICIs) offer a viable treatment option for advanced cervical cancer. The effect of these treatments on patient survival is still unknown despite a large number of trials. The effectiveness and safety of ICI combination therapy for advanced cervical cancer are assessed in this study.MethodsThe PRISMA guidelines were followed when conducting a meta-analysis. A thorough search for literature of four databases (PubMed, Web of Science, Embase, and Cochrane Library) yielded the results. ICI combinations and ICI-based dual combinations were the two types of regimens. Based on PD-L1 expression, baseline patient characteristics, and treatment plan, subgroup analysis was predetermined. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), 18-month PFS rate, treatment-related adverse events (TRAEs), and immune-related adverse events (irAEs) were among the outcomes of interest.ResultsThe analysis includes 18 trials with 4,441 participants. ICI combinations significantly improved OS (HR: 0.69; 95% CI: 0.60 - 0.78) and PFS (HR: 0.68; 95% CI: 0.61 - 0.75), and resulted in a higher ORR (RR: 1.15; 95% CI: 1.06 - 1.24) and DCR (RR: 1.04; 95% CI: 1.01 - 1.06). Dual ICI therapy did not show significant improvement in PFS at 12 months (RR: 1.26; 95% CI: 0.86-1.86), but demonstrated a notable improvement at 18 months (RR: 1.73; 95% CI: 1.04–2.87). The ORR and DCR were comparable between single and dual ICI regimens. Safety was generally well-managed, with a slight increase in adverse events for both combination regimens and dual ICIs. Subgroup analysis revealed that ICB combination therapy resulted in better PFS and OS for PD-L1+ patients, younger patients (< 65 years old), and those with squamous cell carcinoma histology.ConclusionIn patients with advanced cervical cancer, multi-agent regimens that combine chemotherapy, radiation, or targeted therapy with ICIs greatly enhance clinical results while reducing toxicity. Combined ICI therapy could offer a way to overcome resistance, even though it failed to vary significantly from monotherapy in regard to efficacy or safety—a feature that has to be validated by further randomized controlled trials.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD420251266881.