Efficacy and safety of immune checkpoint inhibitors combined with antiangiogenic agents in advanced cervical cancer: a systematic review and meta-analysis.

Background: Advanced cervical cancer (aCC) is associated with a poor prognosis for patients. While immune checkpoint inhibitors (ICIs) have demonstrated potential therapeutic benefits, their effectiveness can be hindered by inherent resistance mechanisms and the onset of immune-related adverse events (irAEs). The strategy of combining ICIs with anti-angiogenic agents has gained traction as a potentially effective treatment approach. Nonetheless, there is a notable absence of robust, systematic evidence to confirm the efficacy and safety of this combination specifically for aCC patients. Methods: We conducted a thorough search of relevant studies across multiple databases, including PubMed, Embase, Cochrane Library, Web of Science, and Scopus. We extracted key outcome measures, such as overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) for further analysis. Results: The analysis included three randomized controlled trials (RCTs;all evaluating first-line treatment for persistent, recurrent, or metastatic cervical cancer) and eight single-arm trials(predominantly later-line or mixed-line settings), encompassing a total of 1, 491 patients. The meta-analysis revealed that in RCTs, ICIs significantly improved OS, decreasing the risk of death by 16% (hazard ratio [HR] = 0.84, 95% confidence interval [CI]:0.78-0.91, P <0.001), and enhanced PFS, reducing the risk of disease progression by 18% (HR = 0.82, 95% CI:0.77-0.88, P <0.001). The combination group exhibited a higher objective response rate (ORR, risk ratio [RR] = 1.19, 95% CI:1.10-1.30, P <0.001) compared to the control group. Findings from single-arm studies provided supportive exploratory evidence, showing a pooled ORR of 0.57 (95% CI: 0.46-0.68).Safety profiles were generally acceptable in RCTs, but the absolute rate of severe toxicity in single-arm studies was substantial (51% grade ≥3).Sensitivity analyses affirmed the robustness of the OS results (I² = 0%), with a stable ORR despite observed heterogeneity. Conclusion: Pooled analysis of first-line RCTs indicates that combining ICIs with anti-angiogenic agents and chemotherapy demonstrates promising efficacy and a manageable safety profile in persistent, recurrent, or metastatic cervical cancer. However, vigilant monitoring and prompt management of immune therapy-related adverse events are crucial for patient safety. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD420251050867.