Investigational New Drugs

, Volume 31, Issue 5, pp 1307–1310 | Cite as

A phase II study of combined VEGF inhibitor (bevacizumab+sorafenib) in patients with metastatic breast cancer: Hoosier Oncology Group Study BRE06-109

  • Lida A. Mina
  • Menggang Yu
  • Cynthia Johnson
  • Cyndi Burkhardt
  • Kathy D. MillerEmail author
  • Robin Zon


Purpose: Angiogenesis plays an essential role in tumor development, invasion and metastasis. We evaluated the efficacy and safety of dual angiogenesis blockade with bevacizumab and sorafenib in patients with metastatic breast cancer. Patients and Methods: Patients who had received no more than 2 prior chemotherapy regimens in any setting were treated with sorafenib 200 mg as a single oral dose daily plus bevacizumab intravenously 5 mg/kg every other week. Response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST). The primary endpoint was progression free survival (PFS). Results: Eighteen patients were enrolled. Median age was 56 yo, all had good performance status KPS of 0 or 1, and 17 patients had received 1 or 2 prior chemotherapy regimens. Median PFS was 2.8 months. There were no complete or partial responses; 3 patients had stable disease for >6 months. Toxicity was substantial with 9 (50 %) patients reporting Grade 3 toxicity. Seven (39 %) patients discontinued therapy due to adverse events including hypertension (N = 2), GI toxicity (N = 1), sensory neuropathy (N = 1), rash (N = 1), pain (N = 1) and wound complication (N = 1). Given the lack of clear efficacy and increased toxicity, accrual was terminated. Conclusion: The combination of sorafenib and bevacizumab has substantial toxicity and minimal efficacy in patients with previously treated metastatic breast cancer. Further study of this combination is not recommended.


Bevacizumab Sorafenib Metastatic breast cancer 


Conflict of interest

Lida A Mina, MD.: No Conflict of Interest

Cynthia S Johnson: No Conflict of Interest

Cynthia Burkhardt: No Conflict of Interest

Menggang Yu: No Conflict of Interest

Robin Zon, MD: No Conflict of Interest

Kathy D Miller, MD: Honoraria to disclose: Yes Genentech

Research funding to disclose: Genentech and Trial supported by Bayer


  1. 1.
    Greenberg PA et al (1996) Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 14:2197–2205CrossRefGoogle Scholar
  2. 2.
    Ferrara N, Davis-Smyth T (1997) The biology of vascular endothelial growth factor. Endocr Rev 18:4–25CrossRefGoogle Scholar
  3. 3.
    Bhardwaj B et al (1996) Localization of platelet-derived growth factor beta receptor expression in the periepithelial stroma of human breast carcinoma. Clin Cancer Res 2:773–782PubMedGoogle Scholar
  4. 4.
    Coltrera MD, Wang J, Porter PL, Gown AM (1995) Expression of platelet-derived growth factor B-chain and the platelet-derived growth factor receptor beta subunit in human breast tissue and breast carcinoma. Cancer Res 55:2703–2708PubMedGoogle Scholar
  5. 5.
    Huang J, Li X, Hilf R, Bambara RA, Muyan M (2005) Molecular basis of therapeutic strategies for breast cancer. Curr Drug Targets Immune Endocr Metabol Disord 5:379–396CrossRefGoogle Scholar
  6. 6.
    Moreno-Aspita A, Hillman D, Wisenfeld TJ, et al (2006) BAY 43–9006 as single oral agent in patients with metastatic breast cancer previously exposed to anthracycline and/or taxane. ASCO abstract 577Google Scholar
  7. 7.
    Baselga J, Gianni L, Gradishar WJ et al (2009) Phase IIb double-blind, randomized, placebo-controlled trials for the efficacy and safety of sorafenib in patients (pts) with metastatic or locally advanced breast cancer (BC): review of the Trials to Investigate the Effects of Sorafenib in BC (TIES) program. Presented at: 2009 ASCO Annual Meeting. Chicago, IL, USA, 4–8 June 2009Google Scholar
  8. 8.
    Gradishar WJ, Kaklamani V, Prasad Sahoo T, et al (2009) A double- blind, randomized, placebo-controlled, phase 2b study evaluating the efficacy and safety of sorafenib (SOR) in combination with paclitaxel (PAC) as a first-line therapy in patients (pts) with locally recurrent or metastatic breast cancer (BC). Presented at: 32nd Annual San Antonio Breast Cancer Symposium. December 10–13, 2009. Abstract 44Google Scholar
  9. 9.
    Baselga J, Grupo Español de Estudio Tratamiento y Otras Estrategias Experimentales en Tumores Sólidos, Roché H et al (2009) SOLTI-0701: A multinational double-blind, randomized Phase IIB study evaluating the efficacy and safety of sorafenib compared to placebo when administered in combination with capecitabine in patients with locally advanced or metastatic breast cancer (BC). Presented at: ECCO 15 and 34th ESMO Multidisciplinary Congress. Berlin, Germany, 20–24 September (2009) (Abstract 3LBA). Updated at: 32nd Annual San Antonio Breast Cancer Symposium. San Antonio, TX, USA, 9–13 December 2009 (Abstract 45). Demonstrates significant activity of sorafenib in combination with capecitabineGoogle Scholar
  10. 10.
    Azad NS et al (2008) Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol 26:3709–3714CrossRefGoogle Scholar
  11. 11.
    Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRefGoogle Scholar
  12. 12.
    Sosman J, Flaherty K, Atkins M et al (2008) Updated results of phase I trial of sorafenib (S) and bevacizumab (B) in patients with metastatic renal cell cancer (mRCC). J Clin Oncol 26(15S):A5011CrossRefGoogle Scholar
  13. 13.
    Feldman DR et al (2009) Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol 27:1432–1439CrossRefGoogle Scholar
  14. 14.
    Mayer EL et al (2010) SABRE-B: an evaluation of paclitaxel and bevacizumab with or without sunitinib as first-line treatment of metastatic breast cancer. Ann Oncol 21:2370–2376CrossRefGoogle Scholar
  15. 15.
    Rini BI et al (2009) A phase I study of sunitinib plus bevacizumab in advanced solid tumors. Clin Cancer Res 15:6277–6283CrossRefGoogle Scholar
  16. 16.
    Socinski MA, Scappaticci FA, Samant M, Kolb MM, Kozloff MF (2010) Safety and efficacy of combining sunitinib with bevacizumab+paclitaxel/carboplatin in non-small cell lung cancer. J Thorac Oncol 5:354–360CrossRefGoogle Scholar

Copyright information

© The Author(s) 2013

Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Authors and Affiliations

  • Lida A. Mina
    • 1
  • Menggang Yu
    • 2
  • Cynthia Johnson
    • 2
  • Cyndi Burkhardt
    • 3
  • Kathy D. Miller
    • 1
    Email author
  • Robin Zon
    • 4
  1. 1.Indiana University Melvin and Bren Simon Cancer CenterIndiana Cancer PavilionIndianapolisUSA
  2. 2.Department of BiostatisticsIndiana University School of MedicineIndianapolisUSA
  3. 3.Hoosier Oncology GroupIndianapolisUSA
  4. 4.Northern Indiana Cancer Research ConsortiumSouth BendUSA

Personalised recommendations