A phase II trial investigating if bevacizumab in combination with hormone therapy will reverse acquired estrogen independence in metastatic breast cancer patients
Document Type
Article
Department
Haematology and Oncology, East Africa
Abstract
Background: Metastatic breast cancer (MBC) remains the second most common cause of cancer death in women in the US. In hormone responsive disease, patients have demonstrated prolonged survival with few side effects, but eventually the cancer becomes resistant to hormone therapy, and cytotoxic chemotherapy with increased toxicity is required. Our Breast Cancer SPORE discovered that increased expression of VEGF caused acquired tamoxifen resistance and tumor loss of estrogen dependence in MCF-7 xenografts. VEGF over- expressing MCF-7 cells displayed increased tumor growth rates and estrogen independence in vivo, and reversal of VEGF over-expression in vivo returned tumors to estrogen dependent growth.
Methods: We hypothesized that adding the anti-VEGF monoclonal antibody, bevacizumab, to hormonal therapy would result in reversal of acquired hormone resistance. This multi-center, open-label, single arm phase II study was designed to evaluate safety and efficacy of this combination. Primary endpoint was time to progression (TTP), and the secondary endpoints were response rate and toxicity. Eligible patients had MBC and had progressed on hormonal therapy after previously responding for at least 6 months.
Results: Planned interim analysis results are reported here. All 19 patients were female with median age of 63 years, and all had ER and/or PR positive MBC. Patients were continued on the same hormone therapy to which they had become refractory, and bevacizumab (15mg/kg IV every 3 weeks) was added. Treatment was stopped early in 3 patients due to a grade 3 leg ulcer, grade 3 hypertension, and grade 3 fatigue, respectively. Overall, the therapy was tolerated well, and no treatment-related deaths or thromboembolic events were seen. Stable disease was documented in 11 (58%) patients, and mean TTP in these patients was 5.8 months (range 1.5 - 12+). There were no complete or partial responses, and 8 (42%) had progression of disease.
Conclusions: Our data suggest that it is safe to combine bevacizumab with hormone therapy in MBC, and this intervention may prolong the TTP without adding adverse side effects. Further investigation utilizing this combination in MBC is warranted.
Publication (Name of Journal)
Journal of Clinical Oncology
DOI
https://doi.org/10.1200/jco.2008.26.15_suppl.1074
Recommended Citation
Falkson, C.,
Rossman, J.,
Nabell, L.,
Carpenter, J.,
Saleh, M.,
O'Malley, J.,
Forero, A.
(2008). A phase II trial investigating if bevacizumab in combination with hormone therapy will reverse acquired estrogen independence in metastatic breast cancer patients. Journal of Clinical Oncology, 26(15).
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/37
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Comments
This work was published before the author joined Aga Khan University.