Iben Kümler1, Ole Grummedal Christiansen2, Dorte Lisbet Nielsen3. 1. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark. Electronic address: iben.kumler@regionh.dk. 2. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark. Electronic address: olegrummedal@gmail.com. 3. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2730 Herlev, Denmark. Electronic address: dorte.nielsen.01@regionh.dk.
Abstract
UNLABELLED: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
UNLABELLED: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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