贝利尤单抗抑制剂治疗晚期或转移性透明细胞肾细胞癌患者的疗效和安全性：一项荟萃分析。

The efficacy and safety of belzutifan inhibitor in patients with advanced or metastatic clear cell renal cell carcinoma: a meta-analysis.

作者信息

Song Ge, Xue Song, Zhu Yingming, Wu Chunling, Ji Xiaowei

机构信息

Department of Critical Care Medicine, Shandong Provincial Maternal and Child Health Care Hospital, Jinan, 250014, China.

Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.

出版信息

BMC Pharmacol Toxicol. 2024 Dec 20;25(1):100. doi: 10.1186/s40360-024-00828-5.

DOI:10.1186/s40360-024-00828-5

PMID:39707485

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11660830/

Abstract

BACKGROUND

The belzutifan is a hypoxia inducible factor-2 alpha (HIF-2α) inhibitor for the treatment of advanced or metastatic clear cell renal cell carcinoma (mccRCC) and has exhibited good safety and efficacy in clinical trials. We conducted a meta-analysis of relevant studies to further clarify the efficacy and safety of belzutifan for the treatment of mccRCC.

METHODS

Multiple databases and abstracts from major scientific meetings were systematically reviewed for eligible articles published before June 1, 2024. The following outcomes were analyzed: objective response rate (ORR), disease control rate (DCR), median duration of response (mDOR), median progression-free survival (mPFS), median overall survival (mOS), and treatment-related adverse events (TRAes). 426 records were reviewed, and data were extracted by at least two individuals.

RESULTS

Seven studies involving 715 patients were included in this meta-analysis. The pooled ORR was 34% (95% confidence interval [CI]: 23-46%), the DCR was 79% (95% CI: 66-90%), the mDOR was 21.8 months (95% CI: 14.82-28.78), and the mPFS time was 8.8 months (95% CI: 6.15-11.44). The pooled incidence of grade 3-5 TRAes was 46%, and the most common TRAe was anemia. Further subgroup analysis revealed that, compared with belzutifan monotherapy, the combination of belzutifan with tyrosine kinase inhibitors (TKIs) as second- or later-line therapy was associated with a statistically significant increase in the ORR. Toxicity was also greater with combined inhibition therapy.

CONCLUSIONS

Our meta-analysis revealed moderate antitumor activity and a manageable safety profile of the inhibitor belzutifan in patients with mccRCC.

摘要

背景

贝利尤单抗是一种缺氧诱导因子-2α（HIF-2α）抑制剂，用于治疗晚期或转移性透明细胞肾细胞癌（mccRCC），并且在临床试验中已显示出良好的安全性和疗效。我们进行了一项相关研究的荟萃分析，以进一步阐明贝利尤单抗治疗mccRCC的疗效和安全性。

方法

系统检索多个数据库以及主要科学会议的摘要，查找2024年6月1日前发表的符合条件的文章。分析以下指标：客观缓解率（ORR）、疾病控制率（DCR）、中位缓解持续时间（mDOR）、中位无进展生存期（mPFS）、中位总生存期（mOS）以及治疗相关不良事件（TRAes）。共筛选426条记录，数据由至少两名研究人员提取。

结果

本荟萃分析纳入了7项研究，共715例患者。汇总的ORR为34%（95%置信区间[CI]：23-46%），DCR为79%（95%CI：66-90%），mDOR为21.8个月（95%CI：14.82-28.78），mPFS时间为8.8个月（95%CI：6.15-11.44）。3-5级TRAes的汇总发生率为46%，最常见的TRAe是贫血。进一步的亚组分析显示，与贝利尤单抗单药治疗相比，贝利尤单抗与酪氨酸激酶抑制剂（TKIs）联合作为二线或更后线治疗可使ORR有统计学意义的增加。联合抑制治疗的毒性也更大。