一线含免疫疗法方案与化疗治疗晚期或转移性尿路上皮癌的疗效和安全性比较：一项随机对照试验的网状荟萃分析

Efficacy and safety of first-line immunotherapy-containing regimens compared with chemotherapy for advanced or metastatic urothelial carcinoma: a network meta-analysis of randomized controlled trials.

作者信息

Liang Weiming, Huang Shibo, Huang Yanping, Huang Miaoyan, Li Chunyan, Liang Yiwen, Pang Li

机构信息

The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, Guangxi, China.

Medicine Center, Guangxi University of Science and Technology, Liuzhou, Guangxi, China.

出版信息

Front Oncol. 2024 Dec 11;14:1453338. doi: 10.3389/fonc.2024.1453338. eCollection 2024.

INTRODUCTION

To assess the efficacy and safety of first-line immunotherapy-containing regimens compared with chemotherapy for advanced or metastatic urothelial carcinoma (UC).

METHOD

A comprehensive search was performed in four databases (Pubmed, Embase, Web of Science, and the Cochrane Library) to identify randomized controlled trials (RCTs) assessing the efficacy of first-line immunotherapy-containing regimens for advanced or metastatic UC. The search encompassed the time span from the inception of the databases to April 23, 2024. A network meta-analysis (NMA) was conducted to assess the rates of progression-free survival (PFS), overall survival (OS), complete response (CR), objective response rate (ORR), and grade ≥ 3 adverse events (AEs).

RESULTS

We conducted a comprehensive analysis of five randomized controlled trials (RCTs) that included a total of 4749 patients. Nine different treatment regimens included in the study were ranked statistically and intuitively using NMA. The top five effective regimens, ranked by OS, were EV + Pembro (1.000), Nivol + Chemo (0.724), Atezo + Chemo (0.610), Durva + Treme (0.558), and Pembro + Chemo (0.530). The top five effective regimens, ranked by PFS, were EV + Pembro (0.999), Nivol + Chemo (0.640), Pembro + Chemo (0.484), Atezo + Chemo (0.373) and Chemo (0.003). The top five effective regimens, ranked by CR, were EV + Pembro (0.969), Nivol + Chemo (0.803), Atezo + Chemo (0.772), Pembro + Chemo (0.472), Durva + Treme (0.449). The top five effective regimens, ranked by ORR, were EV + Pembro (0.995), Nivol + Chemo (0.852), Pembro + Chemo (0.761), Atezo + Chemo (0.623), and Chemo (0.519).

CONCLUSION

Our results indicated that EV + Pembro as first-line therapy resulted in considerably improved efficacy and safety compared to chemotherapy for advanced or metastatic UC. ICI plus chemotherapy as first-line treatment resulted in a longer PFS, a greater ORR, but no longer OS compared to chemotherapy alone, as well as higher toxicity. ICI alone as first-line therapy provided similar OS and lower toxicity compared to chemotherapy, but lower ORR.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/prospero, identifier CRD42024538546.

引言

评估含一线免疫疗法的方案与化疗相比治疗晚期或转移性尿路上皮癌（UC）的疗效和安全性。

方法

在四个数据库（PubMed、Embase、科学网和考科蓝图书馆）中进行全面检索，以识别评估含一线免疫疗法的方案治疗晚期或转移性UC疗效的随机对照试验（RCT）。检索涵盖从各数据库创建至2024年4月23日的时间段。进行网络荟萃分析（NMA）以评估无进展生存期（PFS）、总生存期（OS）、完全缓解（CR）、客观缓解率（ORR）以及≥3级不良事件（AE）的发生率。

结果

我们对五项随机对照试验（RCT）进行了全面分析，这些试验共纳入4749例患者。使用NMA对研究中包含的九种不同治疗方案进行了统计学和直观排序。按OS排序的前五种有效方案为：阿维鲁单抗+帕博利珠单抗（1.000）、纳武利尤单抗+化疗（0.724）、阿替利珠单抗+化疗（0.610）、度伐利尤单抗+曲美替尼（0.558）以及帕博利珠单抗+化疗（0.530）。按PFS排序的前五种有效方案为：阿维鲁单抗+帕博利珠单抗（0.999）、纳武利尤单抗+化疗（0.640）、帕博利珠单抗+化疗（0.484）、阿替利珠单抗+化疗（0.373）以及化疗（0.003）。按CR排序的前五种有效方案为：阿维鲁单抗+帕博利珠单抗（0.969）、纳武利尤单抗+化疗（0.803）、阿替利珠单抗+化疗（0.772）、帕博利珠单抗+化疗（0.472）、度伐利尤单抗+曲美替尼（0.449）。按ORR排序的前五种有效方案为：阿维鲁单抗+帕博利珠单抗（0.995）、纳武利尤单抗+化疗（0.852）、帕博利珠单抗+化疗（0.761）、阿替利珠单抗+化疗（0.623）以及化疗（0.519）。

结论

我们的结果表明，对于晚期或转移性UC，与化疗相比，阿维鲁单抗+帕博利珠单抗作为一线治疗可显著提高疗效和安全性。与单纯化疗相比，免疫检查点抑制剂（ICI）联合化疗作为一线治疗可延长PFS、提高ORR，但OS无延长，且毒性更高。与化疗相比，单独使用ICI作为一线治疗可提供相似的OS且毒性更低，但ORR更低。