Ibibulla Nurbia, Lu Pengfei, Nuerrula Yiliyaer, Hu Xueqin, Aihemaiti Mulati, Wang Yubo, Zhang Hua
Cancer Center, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, China.
Pharmacy Department, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, China.
Front Immunol. 2025 Mar 11;16:1542850. doi: 10.3389/fimmu.2025.1542850. eCollection 2025.
The use of immune checkpoint inhibitors has recently become a promising and innovative therapeutic option for patients suffering from advanced recurrent or metastatic cervical cancer(CC), and several studies of immunotherapy have been published or have revealed stage-by-stage results at international congresses. Nevertheless, there is a lack of meta-analyses of ICIs for advanced CC in past Meta-analysis.
This meta-analysis rigorously followed the PRISMA guidelines, using Review Manager V.5.4 and R(v4.2.2) software for data synthesis. Hazard ratios, risk ratios, and risk differences were calculated, with statistical significance assessed via the Mantel-Haenszel test. Heterogeneity was evaluated using the Higgins I statistic, and sensitivity analyses were conducted if heterogeneity surpassed 50%. The efficacy outcomes examined and gathered included the overall response rate (ORR), progress-free survival, overall survival(OS), and the adverse events (AEs), crucial for understanding the efficacy and safety of ICIs in advanced cervical cancer.
The results demonstrate significant efficacy and manageable safety of ICIs in advanced cervical cancer. In RCTs, ICIs improved OS (HR = 0.66, 95% CI: 0.58-0.75, < 0.00001) and PFS (HR = 0.67, 95% CI: 0.59-0.75, < 0.0001), with a 34% and 33% reduction in death and progression risks, respectively. ORR was higher in ICIs groups (RR = 1.39, 95% CI: 1.08-1.80, = 0.01). Single-arm studies supported these findings (ORR: RD = 0.31, 95% CI: 0.22-0.40, < 0.0001). Safety profiles were manageable, with comparable TRAEs in RCTs and higher incidences in single-arm studies. Subgroup analysis revealed superior OS benefits in PD-L1-positive patients (CPS ≥1, HR = 0.65, 95% CI: 0.50-0.84, = 0.001) and significant efficacy in squamous cell carcinoma (HR = 0.67, < 0.00001). Sensitivity analysis confirmed robust OS results (I² = 0%) and stable ORR despite heterogeneity. Risk of bias was low to moderate.
Our meta-analysis reveals that immune checkpoint inhibitors (ICIs) significantly prolong overall survival in advanced cervical cancer patients, reducing the hazard ratio for death. Despite heterogeneity in outcomes, ICIs offer substantial treatment benefits. Further research is needed to optimize usage and monitor AEs.
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023387789.
免疫检查点抑制剂的使用最近已成为晚期复发性或转移性宫颈癌（CC）患者一种有前景的创新治疗选择，并且多项免疫治疗研究已发表或在国际大会上公布了阶段性结果。然而，过去的荟萃分析中缺乏针对晚期CC的免疫检查点抑制剂的荟萃分析。
本荟萃分析严格遵循PRISMA指南，使用Review Manager V.5.4和R（v4.2.2）软件进行数据合成。计算风险比、风险差值和风险比，通过Mantel-Haenszel检验评估统计学显著性。使用Higgins I统计量评估异质性，如果异质性超过50%则进行敏感性分析。检查和收集的疗效结果包括总缓解率（ORR）、无进展生存期、总生存期（OS）以及不良事件（AE），这些对于了解免疫检查点抑制剂在晚期宫颈癌中的疗效和安全性至关重要。
结果表明免疫检查点抑制剂在晚期宫颈癌中具有显著疗效且安全性可控。在随机对照试验中，免疫检查点抑制剂改善了总生存期（HR = 0.66，95%CI：0.58 - 0.75，P < 0.oooo1）和无进展生存期（HR = 0.67，95%CI：0.59 - 0.75，P < 0.0001），死亡风险和进展风险分别降低了34%和33%。免疫检查点抑制剂组的总缓解率更高（RR = 1.39，95%CI：1.08 - 1.80，P = 0.01）。单臂研究支持了这些发现（总缓解率：RD = 0.31，95%CI：0.22 - 0.40，P < 0.0001）。安全性概况可控，随机对照试验中的治疗相关不良事件相当，单臂研究中的发生率更高。亚组分析显示，程序性死亡受体配体1（PD-L1）阳性患者（综合阳性评分≥1，HR = 0.65，95%CI：0.50 - 0.84，P = 0.001）的总生存期获益更大，鳞状细胞癌患者有显著疗效（HR = 0.67，P < 0.00001）。敏感性分析证实了总生存期结果的稳健性（I² = 0%）以及尽管存在异质性但总缓解率稳定。偏倚风险为低到中度。
我们的荟萃分析表明，免疫检查点抑制剂可显著延长晚期宫颈癌患者的总生存期，降低死亡风险比。尽管结果存在异质性，但免疫检查点抑制剂提供了实质性的治疗益处。需要进一步研究以优化使用方法并监测不良事件。
