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

Background: Locally advanced cervical cancer (LACC) remains a leading cause of cancer-related morbidity and mortality, especially in low- and middle-income countries. While concurrent chemoradiotherapy (CCRT) is the standard of care for LACC, recurrence rates remain high, and the survival outcomes are suboptimal. Recent studies have suggested that immune checkpoint inhibitors (ICIs), such as pembrolizumab and durvalumab, could enhance the therapeutic efficacy of CCRT in LACC patients. Objective: This systematic review and meta-analysis aim to evaluate the efficacy and safety of ICIs in combination with CCRT for patients with LACC. Methods: A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library from inception to November 2025. Randomized controlled trials (RCTs) and prospective cohort studies assessing the use of ICIs (pembrolizumab, durvalumab, atezolizumab) combined with CCRT for LACC were included. Outcomes analyzed included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), complete response (CR), and treatment-related adverse events (AEs). Results: Data from five studies involving 1,987 patients were pooled. The addition of ICIs to CCRT significantly improved PFS (HR = 0.76, 95% CI: 0.64-0.91) and ORR (OR = 1.28, 95% CI: 1.06-1.56). Although the CR rate showed an improving trend, it did not reach statistical significance. Immune-related AEs (irAEs) were more common with ICI use (OR = 3.00, 95% CI: 1.68-5.34), but they were generally manageable. Severe irAEs leading to treatment discontinuation occurred in 5%-7% of patients. Conclusion: This meta-analysis supports the combination of ICIs with CCRT as an effective treatment strategy for LACC, improving PFS and ORR without a significant increase in severe toxicity. However, further studies with mature OS data and exploration of optimal ICI timing are warranted.