Immune checkpoint therapy in locally advanced, persistent, recurrent, and metastatic cervical cancer: A systematic review and Bayesian network meta-analysis.

[BACKGROUND] Cervical cancer is the fourth most common malignancy among women worldwide. Despite curative-intent treatment, 10%-30% of patients experience treatment failure due to persistent or recurrent disease within five years. Immune checkpoint inhibitors (ICIs) have shown clinical benefit in phase 3 trials, yet no head-to-head comparisons exist between ICIs.

[OBJECTIVES] This study aimed to assess and compare the efficacy of ICIs in patients with locally advanced and persistent, recurrent, or metastatic cervical cancer.

[SEARCH STRATEGY] We conducted a systematic review and Bayesian network meta-analysis following PRISMA guidelines (PROSPERO: CRD420251056382). The databases of PubMed, Scopus, Google Scholar, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were systematically searched by two independent reviewers.

[SELECTION CRITERIA] Eligibility criteria were defined by the PICOS framework: (1) Population: patients with locally advanced, persistent, recurrent, or metastatic cervical cancer. (2) Intervention: ICI plus standard therapy. (3) Comparator: standard therapy with placebo. (4) Outcomes: overall survival (OS) and progression-free survival (PFS). (5) Study design: phase 3 randomized controlled trials (RCTs).

[DATA COLLECTION AND ANALYSIS] Surface under the cumulative ranking curve (SUCRA) rankings were used to determine comparative efficacy. Risk of bias was assessed using RoB 2, and certainty of evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE).

[MAIN RESULTS] Five phase 3 RCTs were included. Two studies evaluated patients with locally advanced disease (n = 1830), comparing concurrent chemoradiotherapy (CCRT) with or without ICIs. Three studies included patients with persistent, recurrent, or metastatic disease (n = 1472), comparing systemic chemotherapy with or without ICIs. In locally advanced disease, pembrolizumab added to CCRT showed better OS and PFS results compared to CCRT alone, and SUCRA rankings placed it above the regimen containing durvalumab. In the advanced disease setting, pembrolizumab plus chemotherapy improved OS and PFS overall compared to other ICIs, especially in patients receiving bevacizumab. Subgroup analyses suggested cadonilimab may offer superior outcomes in non-metastatic patients.

[CONCLUSIONS] Pembrolizumab ranked highest in OS and PFS among patients with locally advanced or advanced cervical cancer. These findings support its preferential use over other ICIs. However, direct head-to-head trials are needed to validate these results and inform optimal ICI selection.