Analysis of Early Hypertension and Clinical Outcome With Bevacizumab: Results From Seven Phase III Studies
Analysis of Early Hypertension and Clinical Outcome With Bevacizumab: Results From Seven Phase III Studies
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DOI：
10.1634/theoncologist.2012-0339
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发表时间：
2013-03-01
期刊：
影响因子：
5.8
通讯作者：
Rosen, Oliver
中科院分区：
文献类型：
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作者：
Hurwitz, Herbert I.;Douglas, Pamela S.;Rosen, Oliver
背景高血压与抗血管内皮生长因子治疗相关，但高血压的临床意义尚不确定。为了评估贝伐珠单抗相关高血压的预后和预测价值，对7项公司申办的贝伐珠单抗安慰剂对照III期研究进行了高血压和疗效结局是否相关的综合分析。患者特异性数据来自6，486例转移性结直肠癌、乳腺癌、非小细胞肺癌、胰腺癌和肾细胞癌患者。原发性高血压终点是在治疗的前60天内收缩压（BP）升高>20 mmHg或舒张压>10 mmHg。其他终点包括血压变化的其他预定义阈值和使用美国国家癌症研究所不良事件通用术语标准分级的高血压严重程度。为了分析早期血压升高的一般预后重要性，使用多变量考克斯回归模型评估对照组中血压变化与无进展（PFS）和总生存期（OS）结局之间的相关性。为了分析早期血压升高是否可以预测贝伐单抗的获益，在贝伐单抗治疗组和对照组中进行了类似的分析。在7项研究中的6项中，早期血压升高既不能预测贝伐单抗的临床获益，也不能预测疾病的病程。在AVF 2107 g研究中，贝伐珠单抗组早期血压升高与PFS和OS时间延长相关，而对照组与OS时间缩短相关。根据PFS或OS结局，早期治疗相关BP升高不能预测贝伐珠单抗的临床获益。血压升高似乎对晚期癌症患者的预后没有普遍意义。肿瘤学家2013;18：273-280
Background. Hypertension is associated with antivascular endothelial growth factor treatment, but the clinical implications of hypertension are uncertain. To assess the prognostic and predictive value of bevacizumab-related hypertension, a comprehensive analysis of whether hypertension and efficacy outcomes are associated was conducted on seven company-sponsored placebo-controlled phase III studies of bevacizumab.Methods. Patient-specific data were available from 6,486 patients with metastatic colorectal, breast, non-small cell lung, pancreatic, and renal cell cancers. Primary hypertension endpoint was a blood pressure (BP) increase of >20 mmHg systolic or >10 mmHg diastolic within the first 60 days of treatment. Additional endpoints included other predefined thresholds of change in BP and severity of hypertension graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events. To analyze the general prognostic importance of an early BP increase, multivariate Cox regression models were used to assess the correlation between BP changes and progression-free (PFS) and overall survival (OS) outcomes in the control groups. To analyze whether early BP increases could predict for benefit from bevacizumab, similar analyses were conducted in the bevacizumab treated and control groups.Results. In six of seven studies, early BP increase was neither predictive of clinical benefit from bevacizumab nor prognostic for the course of the disease. For study AVF2107g, early increased BP was associated with longer PFS and OS times in the bevacizumab group but shorter OS time in the control group.Conclusions. Early treatment-related BP increases do not predict clinical benefit from bevacizumab based on PFS or OS outcomes. BP increases do not appear to have general prognostic importance for patients with advanced cancer. The Oncologist 2013;18:273-280