360
Views
3
CrossRef citations to date
0
Altmetric
Drug Evaluation

Clinical results of randomized trials and ‘real-world’ data exploring the impact of Bevacizumab for breast cancer: opportunities for clinical practice and perspectives for research

, , , , , , , , , , , & show all
Pages 497-506 | Received 24 Nov 2016, Accepted 27 Jan 2017, Published online: 13 Feb 2017

References

  • Cardoso F, Costa A, Senkus E, et al. 3rd ESO-ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3). Ann Oncol. 2016;mdw544. [Epub ahead of print].
  • Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182–1186.
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674.
  • Baeriswyl V, Christofori G. The angiogenic switch in carcinogenesis. Semin Cancer Biol. 2009;19:329–337.
  • Pouyssegur J, Dayan F, Mazure NM. Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature. 2006;441:437–443.
  • Shannon AM, Bouchier-Hayes DJ, Condron CM, et al. Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev. 2003;29:297–307.
  • Unwith S, Zhao H, Hennah L, et al. The potential role of HIF on tumour progression and dissemination. Int J Cancer. 2015;136:2491–2503.
  • Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 2002;20:4368–4380.
  • Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–676.
  • Ferrara N, Hillan KJ, Gerber HP, et al. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004;3:391–400.
  • Presta LG, Chen H, O’Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997;57:4593–4599.
  • Borgstrom P, Gold DP, Hillan KJ, et al. Importance of VEGF for breast cancer angiogenesis in vivo: implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin. Anticancer Res. 1999;19:4203–4214.
  • Marty M, Pivot X. The potential of anti-vascular endothelial growth factor therapy in metastatic breast cancer: clinical experience with anti-angiogenic agents, focusing on bevacizumab. Eur J Cancer. 2008;44:912–920.
  • Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 2001;19:843–850.
  • Margolin K, Gordon MS, Holmgren E, et al. Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: pharmacologic and long-term safety data. J Clin Oncol. 2001;19:851–856.
  • Cobleigh MA, Langmuir VK, Sledge GW, et al. A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol. 2003;30:117–124.
  • Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005;23:792–799.
  • Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666–2676.
  • Miles DW, Chan A, Dirix LY, et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010;28:3239–3247.
  • Robert NJ, Dieras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011;29:1252–1260.
  • Zielinski C, Lang I, Inbar M, et al. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. Lancet Oncol. 2016;17:1230–1239.
  • Gligorov J, Doval D, Bines J, et al. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:1351–1360.
  • Brufsky AM, Hurvitz S, Perez E, et al. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011;29:4286–4293.
  • Vrdoljak E, Marschner N, Zielinski C, et al. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol. 2016;27:2046–2052.
  • Miles DW, Dieras V, Cortes J, et al. First-line bevacizumab in combination with chemotherapy for HER2-negative metastatic breast cancer: pooled and subgroup analyses of data from 2447 patients. Ann Oncol. 2013;24:2773–2780.
  • Rossari JR, Metzger-Filho O, Paesmans M, et al. Bevacizumab and breast cancer: a meta-analysis of first-line phase III studies and a critical reappraisal of available evidence. J Oncol. 2012;2012:417673.
  • Valachis A, Polyzos NP, Patsopoulos NA, et al. Bevacizumab in metastatic breast cancer: a meta-analysis of randomized controlled trials. Breast Cancer Res Treat. 2010;122:1–7.
  • Cuppone F, Bria E, Vaccaro V, et al. Magnitude of risks and benefits of the addition of bevacizumab to chemotherapy for advanced breast cancer patients: meta-regression analysis of randomized trials. J Exp Clin Cancer Res. 2011;30:54.
  • Lee JB, Woo OH, Park KH, et al. Bevacizumab for salvage treatment of metastatic breast cancer: a systemic review and meta-analysis of randomized controlled trials. Invest New Drugs. 2011;29:182–188.
  • Wagner AD, Thomssen C, Haerting J, et al. Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer. Cochrane Database Syst Rev. 2012;CD008941.
  • Von Minckwitz G, Puglisi F, Cortes J, et al. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15:1269–1278.
  • Brufsky A, Hoelzer K, Beck T, et al. A randomized phase II study of paclitaxel and bevacizumab with and without gemcitabine as first-line treatment for metastatic breast cancer. Clin Breast Cancer. 2011;11:211–220.
  • Dieras V, Campone M, Yardley DA, et al. Randomized, phase II, placebo-controlled trial of onartuzumab and/or bevacizumab in combination with weekly paclitaxel in patients with metastatic triple-negative breast cancer. Ann Oncol. 2015;26:1904–1910.
  • Lam SW, De Groot SM, Honkoop AH, et al. Paclitaxel and bevacizumab with or without capecitabine as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: a multicentre, open-label, randomised phase 2 trial. Eur J Cancer. 2014;50:3077–3088.
  • Luck HJ, Lubbe K, Reinisch M, et al. Phase III study on efficacy of taxanes plus bevacizumab with or without capecitabine as first-line chemotherapy in metastatic breast cancer. Breast Cancer Res Treat. 2015;149:141–149.
  • Mayer EL, Dhakil S, Patel T, et al. SABRE-B: an evaluation of paclitaxel and bevacizumab with or without sunitinib as first-line treatment of metastatic breast cancer. Ann Oncol. 2010;21:2370–2376.
  • Yardley DA, Bosserman LD, O’Shaughnessy JA, et al. Paclitaxel, bevacizumab, and everolimus/placebo as first-line treatment for patients with metastatic HER2-negative breast cancer: a randomized placebo-controlled phase II trial of the sarah cannon research institute. Breast Cancer Res Treat. 2015;154:89–97.
  • Dieras V, Wildiers H, Jassem J, et al. Trebananib (AMG 386) plus weekly paclitaxel with or without bevacizumab as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer: A phase 2 randomized study. Breast. 2015;24:182–190.
  • Liu X, Liu X, Qiao T, et al. Efficacy and safety of adding an agent to bevacizumab/taxane regimens for the first-line treatment of Her2-negative patients with locally recurrent or metastatic breast cancer: results from seven randomized controlled trials. Onco Targets Ther. 2016;9:3771–3781.
  • Smith IE, Pierga JY, Biganzoli L, et al. First-line bevacizumab plus taxane-based chemotherapy for locally recurrent or metastatic breast cancer: safety and efficacy in an open-label study in 2,251 patients. Ann Oncol. 2011;22:595–602.
  • Smith I, Pierga JY, Biganzoli L, et al. Final overall survival results and effect of prolonged (>/= 1 year) first-line bevacizumab-containing therapy for metastatic breast cancer in the ATHENA trial. Breast Cancer Res Treat. 2011;130:133–143.
  • Delaloge S, Perol D, Courtinard C, et al. Paclitaxel plus bevacizumab or paclitaxel as first-line treatment for HER2-negative metastatic breast cancer in a multicenter national observational study. Ann Oncol. 2016;27:1725–1732.
  • Mueller V, Dank M, De Ducla S, et al. Real-world effectiveness and safety of first-line bevacizumab (BEV) + paclitaxel (PAC) in >2000 patients (pts) with HER2-negative metastatic breast cancer (mBC). Ann Oncol. 2016;27: (suppl_6): 237P. ESMO Meeting Abstract.
  • Roy V, Perez EA. Biologic therapy of breast cancer: focus on co-inhibition of endocrine and angiogenesis pathways. Breast Cancer Res Treat. 2009;116:31–38.
  • Martin M, Loibl S, Von Minckwitz G, et al. Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study. J Clin Oncol. 2015;33:1045–1052.
  • Haba J, Aguilar EA, Morales S, et al. ACE and CXCL10 as predictive biomarkers in the LEA study. Ann Oncol. 2016;27 (suppl_6): 135P. ESMO Meeting Abstract. .
  • Dickler MN, Barry WT, Cirrincione CT, et al. Phase III trial evaluating letrozole as first-line endocrine therapy with or without bevacizumab for the treatment of postmenopausal women with hormone receptor-positive advanced-stage breast cancer: CALGB 40503 (Alliance). J Clin Oncol. 2016;34:2602–2609.
  • Carbognin L, Sperduti I, Ciccarese M, et al. Prognostic model for advanced breast carcinoma with luminal subtype and impact of hormonal maintenance: implications for post-progression and conditional survival. Breast. 2016;29:24–30.
  • Dufresne A, Pivot X, Tournigand C, et al. Maintenance hormonal treatment improves progression free survival after a first line chemotherapy in patients with metastatic breast cancer. Int J Med Sci. 2008;5:100–105.
  • Militello L, Carli P, Di Lauro V, et al. Bevacizumab as maintenance therapy (mBev) in metastatic breast cancer (MBC). ASCO Meet Abstr. 2013;31:e22149.
  • Tredan O, Follana P, Moullet I, et al. A phase III trial of exemestane plus bevacizumab maintenance therapy in patients with metastatic breast cancer after first-line taxane and bevacizumab: a GINECO group study. Ann Oncol. 2016;27:1020–1029.
  • Konecny GE, Meng YG, Untch M, et al. Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res. 2004;10:1706–1716.
  • Yang W, Klos K, Yang Y, et al. ErbB2 overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human breast carcinoma. Cancer. 2002;94:2855–2861.
  • Pegram MD YC, Ku NC, et al. Phase I combined biological therapy of breast cancer using two humanized monoclonal antibodies directed against HER-2 proto-oncogene and vascular endothelial growth factor (VEGF). Breast Cancer Res Treat. 2004;88(suppl 1; abstr 30–39):S124.
  • Martin M, Makhson A, Gligorov J, et al. Phase II study of bevacizumab in combination with trastuzumab and capecitabine as first-line treatment for HER-2-positive locally recurrent or metastatic breast cancer. Oncologist. 2012;17:469–475.
  • Schwartzberg LS, Badarinath S, Keaton MR, et al. Phase II multicenter study of docetaxel and bevacizumab with or without trastuzumab as first-line treatment for patients with metastatic breast cancer. Clin Breast Cancer. 2014;14:161–168.
  • Lin NU, Seah DS, Gelman R, et al. A phase II study of bevacizumab in combination with vinorelbine and trastuzumab in HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2013;139:403–410.
  • Gianni L, Romieu GH, Lichinitser M, et al. AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013;31:1719–1725.
  • Arteaga CL, Mayer IA, O’Neill AM, et al. A randomized phase III double-blinded placebo-controlled trial of first-line chemotherapy and trastuzumab with or without bevacizumab for patients with HER2/neu-overexpressing metastatic breast cancer (HER2+ MBC): A trial of the Eastern Cooperative Oncology Group (E1105). ASCO Meet Abstr. 2012;30:605.
  • Drooger JC, Van Tinteren H, Sm DG, et al. A randomized phase 2 study exploring the role of bevacizumab and a chemotherapy-free approach in HER2-positive metastatic breast cancer: the HAT study (BOOG 2008-2003), a Dutch breast cancer research group trial. Cancer. 2016;122:2961–2970.
  • Hurvitz S. Final results of a phase II trial evaluating trastuzumab and bevacizumab as first line treatment of HER2-amplified advanced breast cancer. Cancer Res. 2009;69(24 Suppl):abstract nr 6094.
  • Rugo HS, Chien AJ, Franco SX, et al. A phase II study of lapatinib and bevacizumab as treatment for HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat. 2012;134:13–20.
  • Carbognin L, Furlanetto J, Vicentini C, et al. Neoadjuvant strategies for triple negative breast cancer: ‘state-of-the-art’ and future perspectives. Anticancer Agents Med Chem. 2015;15:15–25.
  • Golshan M, Garber JE, Gelman R, et al. Does neoadjuvant bevacizumab increase surgical complications in breast surgery? Ann Surg Oncol. 2011;18:733–737.
  • Gerber B, Loibl S, Eidtmann H, et al. Neoadjuvant bevacizumab and anthracycline-taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the geparquinto study (GBG 44). Ann Oncol. 2013;24:2978–2984.
  • Von Minckwitz G, Eidtmann H, Rezai M, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012;366:299–309.
  • Sikov WM, Berry DA, Perou CM, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015;33:13–21.
  • Nahleh ZA, Barlow WE, Hayes DF, et al. SWOG S0800 (NCI CDR0000636131): addition of bevacizumab to neoadjuvant nab-paclitaxel with dose-dense doxorubicin and cyclophosphamide improves pathologic complete response (pCR) rates in inflammatory or locally advanced breast cancer. Breast Cancer Res Treat. 2016;158:485–495.
  • Bear HD, Tang G, Rastogi P, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012;366:310–320.
  • Von Minckwitz G, Loibl S, Untch M, et al. Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)dagger. Ann Oncol. 2014;25:2363–2372.
  • Earl HM, Hiller L, Dunn JA, et al. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol. 2015;16:656–666.
  • Bertucci F, Fekih M, Autret A, et al. Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2016;17:600–611.
  • Coudert B, Pierga JY, Mouret-Reynier MA, et al. Use of [(18)F]-FDG PET to predict response to neoadjuvant trastuzumab and docetaxel in patients with HER2-positive breast cancer, and addition of bevacizumab to neoadjuvant trastuzumab and docetaxel in [(18)F]-FDG PET-predicted non-responders (AVATAXHER): an open-label, randomised phase 2 trial. Lancet Oncol. 2014;15:1493–1502.
  • Steger GG, Greil R, Hubalek M, et al. Abstract P3-11-06: bevacizumab in combination with docetaxel+trastuzumab +/- non-pegylated liposomal doxorubicin: final results of ABCSG-32, a prospective, randomized phase II-study. Cancer Res. 2015;75:P3-11-06-P13-11-06.
  • Smith JW 2nd, Buyse ME, Rastogi P, et al. Epirubicin with cyclophosphamide followed by docetaxel with trastuzumab and bevacizumab as neoadjuvant therapy for HER2-positive locally advanced breast cancer or as adjuvant therapy for HER2-positive pathologic stage III breast cancer: a phase II trial of the NSABP foundation research group, FB-5. Clin Breast Cancer. 2016 Jul 28. [Epub ahead of print]..
  • Pierga JY, Petit T, Delozier T, et al. Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study. Lancet Oncol. 2012;13:375–384.
  • Cao L, Yao GY, Liu MF, et al. Neoadjuvant bevacizumab plus chemotherapy versus chemotherapy alone to treat non-metastatic breast cancer: a meta-analysis of randomised controlled trials. Plos One. 2015;10:e0145442.
  • Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1995;1:149–153.
  • Kumler I, Christiansen OG, Nielsen DL. A systematic review of bevacizumab efficacy in breast cancer. Cancer Treat Rev. 2014;40:960–973.
  • Cameron D, Brown J, Dent R, et al. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet Oncol. 2013;14:933–942.
  • Slamon DJ SS, Swain SM, Buyse M, et al. Primary results from BETH, a phase 3 controlled study of adjuvant chemotherapy and trastuzumab ± bevacizumab in patients with HER2-positive, node-positive or high risk node-negative breast cancer. Cancer Res. 2013;73(24 suppl):abstract nr S1–03.
  • Miller KOA. Dang CT. Bevacizumab (Bv) in the adjuvant treatment of HER2-negative breast cancer: final results from Eastern cooperative oncology group E5103. J Clin Oncol. 2014;32(5s):suppl; abstr 500.
  • Cortes J, Calvo V, Ramirez-Merino N, et al. Adverse events risk associated with bevacizumab addition to breast cancer chemotherapy: a meta-analysis. Ann Oncol. 2012;23:1130–1137.
  • Bear HD, Tang G, Rastogi P, et al. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015;16:1037–1048.
  • Miles D, Cameron D, Bondarenko I, et al. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer. 2017 Jan;70:146–155.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.