Comparison of drug regimens for recurrent or metastatic cervical cancer: a systematic review and network meta-analysis.

[BACKGROUND] Cervical cancer is one of the most common cancers among women worldwide. For patients with recurrent or metastatic cervical cancer (R/MCC) after surgery or radiotherapy, drug therapy is the primary treatment modality. Currently, head-to-head comparison studies of different immune checkpoint inhibitors (ICI) combination regimens are lacking in clinical practice. This study aims to provide an indirect comparison of the relative efficacy of various drug regimens (including chemotherapy, targeted therapy, and immunotherapy) for R/MCC patients through a systematic review and network meta-analysis (NMA).

[METHOD] The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines and systematically searched databases including PubMed, Web of Science, Embase and the Cochrane Library for randomized controlled trials (RCTs) comparing drug treatment regimens. The primary efficacy endpoint was overall survival (OS). Progression-free survival (PFS) was analyzed as a econdary endpoint to provide additional evidence of clinical activity. We conducted the NMA using a Bayesian random-effects model, estimated the ranking of each treatment regimen via the Surface Under the Cumulative Ranking Curve (SUCRA), and performed a Frequentist NMA as a sensitivity analysis.

[RESULT] A total of 15 RCTs involving 4,588 R/MCC patients were included. The NMA results for OS showed that ICI combination regimens (with or without bevacizumab) provided a significant benefit compared to backbone chemotherapy. Specifically, the regimen of pembrolizumab plus chemotherapy and bevacizumab showed the greatest potential for OS benefit (Frequentist HR: 0.45, 95%CI: 0.30-0.67 vs. cisplatin plus paclitaxel), ranking first by SUCRA (87%). Among traditional chemotherapy regimens, only the cisplatin plus paclitaxel regimen was significantly superior to single-agent cisplatin (Frequentist HR: 0.74, 95%CI: 0.59-0.93). The NMA results for PFS indicated that the cadonilimab plus chemotherapy regimen was the most outstanding (Frequentist HR: 0.46, 95%CI: 0.32-0.66 vs. cisplatin plus paclitaxel), ranking first by SUCRA (90%). The rankings of the treatment regimens were consistent across both Bayesian and Frequentist, suggesting strong robustness of the results.

[CONCLUSION] ICI combination regimens (with or without bevacizumab) are likely the optimal choice for treating R/MCC patients. Pembrolizumab plus chemotherapy and bevacizumab is most likely to yield the OS benefit, and cisplatin plus paclitaxel remains the best backbone chemotherapy regimen for R/MCC. This study provides comprehensive indirect comparison evidence for clinicians in selecting R/MCC treatment strategies.

[SYSTEMATIC REVIEW REGISTRATION] https://www.crd.york.ac.uk/PROSPERO/view/CRD420251180897, identifier CRD42024604107.