Roviello Giandomenico, Bachelot Thomas, Hudis Clifford A, Curigliano Giuseppe, Reynolds Andrew R, Petrioli Roberto, Generali Daniele
Department of Oncology, Medical Oncology Unit, San Donato Hospital, Via Nenni 20, 52100 Arezzo, Italy; Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129 Trieste, Italy.
Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
Eur J Cancer. 2017 Apr;75:245-258. doi: 10.1016/j.ejca.2017.01.026. Epub 2017 Feb 24.
Bevacizumab is a humanised monoclonal antibody which blocks the binding of circulating vascular endothelial growth factor to its receptors. To date, the Food and Drug Administration has approved bevacizumab for the treatment of several solid tumours. To assess the impact of bevacizumab-based regimens on outcome in these advanced solid tumour types, we performed a meta-analysis. We included all of the randomised trials (phase II or III) where bevacizumab was tested in the first line setting compared with a control arm, including chemotherapy, placebo or other anti-neoplastic agents.
A literature-based meta-analysis of randomised controlled trials (RCTs) in accordance with the preferences for reported items in systematic reviews and meta-analyses guidelines were undertaken. The primary end-point considered was overall survival (OS). The secondary end-points were progression-free survival (PFS) time, response rate and safety. A subgroup analysis was performed to highlight any differences between studies in different tumour types for all end-points.
The pooled analysis from RCTs on bevacizumab-based regimens revealed significantly increased OS (hazard ratio [HR] for death 0.92, 95% confidence interval [CI]: 0.88-0.95; P < 0.0001), PFS (HR: 0.72, 95% CI: 0.67-0.78; P < 0.00001) and response rate (risk ratio: 1.38, 95% CI: 1.27-1.50; P < 0.00001) compared to control arm in solid tumours overall and in colorectal, lung, ovarian and renal cancer as single indications. However, notably, no effect on survival was seen in breast cancer.
This study confirmed that bevacizumab-based regimens result in a significant effect on survival and response in advanced colorectal, lung, ovarian and kidney cancer. In cancers where bevacizumab failed overall as in breast cancer, a dedicated biomarkers analysis is warranted to select the proper subgroup of patient that might have the adequate clinical benefit.
贝伐单抗是一种人源化单克隆抗体,可阻断循环血管内皮生长因子与其受体的结合。迄今为止,美国食品药品监督管理局已批准贝伐单抗用于治疗多种实体瘤。为评估基于贝伐单抗的治疗方案对这些晚期实体瘤类型预后的影响,我们进行了一项荟萃分析。我们纳入了所有将贝伐单抗与对照组(包括化疗、安慰剂或其他抗肿瘤药物)进行一线治疗对比测试的随机试验(II期或III期)。
根据系统评价和荟萃分析指南中报告项目的偏好,对随机对照试验(RCT)进行基于文献的荟萃分析。所考虑的主要终点是总生存期(OS)。次要终点是无进展生存期(PFS)时间、缓解率和安全性。进行亚组分析以突出不同肿瘤类型研究在所有终点上的任何差异。
基于贝伐单抗治疗方案的RCT汇总分析显示,与总体实体瘤以及作为单一适应症的结直肠癌、肺癌、卵巢癌和肾癌的对照组相比,总生存期(死亡风险比[HR]为0.92,95%置信区间[CI]:0.88 - 0.95;P < 0.0001)、无进展生存期(HR:0.72,95% CI:0.67 - 0.78;P < 0.00001)和缓解率(风险比:1.38,95% CI:1.27 - 1.50;P < 0.00001)均显著增加。然而,值得注意的是,在乳腺癌中未观察到对生存期的影响。
本研究证实,基于贝伐单抗的治疗方案对晚期结直肠癌、肺癌、卵巢癌和肾癌的生存期和缓解有显著影响。在贝伐单抗总体治疗失败的癌症(如乳腺癌)中,有必要进行专门的生物标志物分析,以选择可能具有足够临床获益的合适患者亚组。