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高血压作为贝伐单抗治疗转移性结直肠癌疗效的预测生物标志物:一项荟萃分析。

Hypertension as a predictive biomarker for efficacy of bevacizumab treatment in metastatic colorectal cancer: a meta-analysis.

作者信息

Chen Cui, Sun Peng, Ye Sheng, Weng Hui-Wen, Dai Qiang-Sheng

机构信息

Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

J BUON. 2014 Oct-Dec;19(4):917-24.

Abstract

PURPOSE

Bevacizumab has demonstrated survival benefit in patients with metastatic colorectal cancer (mCRC) when combined with chemotherapy. However, no validated predictors currently exist for its efficacy. Hypertension has been evaluated as a surrogate marker for efficacy of bevacizumab, although analyses, to date, have yielded conflicting results. The aim of this meta-analysis was to dissect the association between hypertension and efficacy of bevacizumab treatment in mCRC.

METHODS

We searched PubMed, EMBASE, Chinese Biomedical Database (CBM), and Wan Fang Digital Journals before September, 2013. The primary clinical outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Relative risk (RR) or summary hazard ratio (HR) were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies. Studies meeting our search criteria were assessed.

RESULTS

Nine studies were considered eligible, with 1674 mCRC patients included. Six (308 patients, 104 with hypertension), 8 (1661 patients, 431 with hypertension) and 5 (1512 patients, 408 with hypertension) studies were eligible for the ORR, PFS and OS meta-analysis, respectively. Bevacizumab-related hypertension was associated with increased ORR (RR= 1.63; 95% CI 1.26-2.12; p=0.0002), improved PFS (HR=0.68; 95% CI 0.58-0.79; p<0.00001) and OS (HR=0.52; 95% CI 0.42-0.66; p<0.00001). There was no statistically significant difference between-study heterogeneity.

CONCLUSION

These analyses suggest that hypertension may be a potential biomarker for efficacy of bevacizumab treatment in mCRC. Additional large prospective trials are required to confirm its predictive role.

摘要

目的

贝伐单抗与化疗联合应用时已显示出对转移性结直肠癌(mCRC)患者有生存获益。然而,目前尚无经证实的疗效预测指标。高血压已被评估为贝伐单抗疗效的替代标志物,尽管迄今为止的分析结果相互矛盾。本荟萃分析的目的是剖析高血压与mCRC患者贝伐单抗治疗疗效之间的关联。

方法

我们检索了2013年9月之前的PubMed、EMBASE、中国生物医学数据库(CBM)和万方数字期刊。主要临床结局包括客观缓解率(ORR)、无进展生存期(PFS)和总生存期(OS)。根据纳入研究的异质性,使用固定效应或随机效应模型计算相对风险(RR)或汇总风险比(HR)。对符合我们检索标准的研究进行评估。

结果

9项研究被认为符合条件,共纳入1674例mCRC患者。分别有6项(308例患者,104例有高血压)、8项(1661例患者,431例有高血压)和5项(1512例患者,408例有高血压)研究符合ORR、PFS和OS荟萃分析的条件。与贝伐单抗相关的高血压与ORR升高(RR = 1.63;95%CI 1.26 - 2.12;p = 0.0002)、PFS改善(HR = 0.68;95%CI 0.58 - 0.79;p < 0.00001)和OS改善(HR = 0.52;95%CI 0.42 - 0.66;p < 0.00001)相关。研究间异质性无统计学显著差异。

结论

这些分析表明,高血压可能是mCRC患者贝伐单抗治疗疗效的潜在生物标志物。需要更多大型前瞻性试验来证实其预测作用。

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