Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Cancer Treat Rev. 2014 Sep;40(8):960-73. doi: 10.1016/j.ctrv.2014.05.006. Epub 2014 May 22.
Angiogenesis is a key component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for the treatment of cancer. We systematically describe phase II and III clinical trials of bevacizumab for the treatment of breast cancer.
A computer-based literature search was carried out using PUBMED and conference databases. Original phase II and III studies reporting ≥15 patients who received bevacizumab were included.
41 phase II trials were identified in the metastatic setting. Most trials found bevacizumab treatment feasible. Response rates (RR) varied from 0% to 76.5%, time to progression (TTP)/progression free survival (PFS) from 2.4 to 25.3 months and overall survival from 11.5 to more than 38 months. 14 phase III trials including more than 4400 patients with MBC unanimously showed increased RR and PFS, however, no trials demonstrated an OS benefit. In the neoadjuvant setting 23 phase II and III trials were identified. All studies found increased pCR/tpCR but no benefit in terms of OS could be demonstrated. The only study conducted in the adjuvant setting failed to show any survival benefit of bevacizumab.
Despite increased response rates in both the metastatic and neoadjuvant setting, bevacizumab has failed to show any OS benefit. Future trials should include identification of robust predictive biomarkers in order to improve our understanding of molecular biomarkers and mechanisms.
血管生成是癌症生长、侵袭和转移的关键组成部分。因此,抑制血管生成是治疗癌症的一种有吸引力的策略。我们系统地描述了贝伐单抗治疗乳腺癌的 II 期和 III 期临床试验。
使用 PUBMED 和会议数据库进行了基于计算机的文献检索。纳入了报告≥15 名接受贝伐单抗治疗的患者的原始 II 期和 III 期研究。
在转移性环境中确定了 41 项 II 期试验。大多数试验发现贝伐单抗治疗是可行的。缓解率(RR)从 0%到 76.5%不等,无进展生存期(TTP)/无进展生存期(PFS)从 2.4 到 25.3 个月,总生存期从 11.5 个月以上。包括 4400 多名 MBC 患者的 14 项 III 期试验一致显示 RR 和 PFS 增加,但没有试验显示 OS 获益。在新辅助环境中确定了 23 项 II 期和 III 期试验。所有研究都发现 pCR/tpCR 增加,但 OS 无获益。唯一在辅助环境中进行的研究未能显示贝伐单抗的任何生存获益。
尽管转移性和新辅助环境中的缓解率都有所增加,但贝伐单抗未能显示任何 OS 获益。未来的试验应包括识别强大的预测生物标志物,以提高我们对分子生物标志物和机制的理解。