Update of a phase II trial of bevacizumab in combination with hormonal therapy to reverse acquired estrogen independence in metastatic breast cancer patients

Abstract

e12027 Background: Metastatic breast cancer (MBC) remains the second most common cause of cancer death in women in the US. More than 80% of breast cancers are potentially hormone responsive, but resistance eventually precludes cure. Various mechanisms of acquired hormone resistance have been postulated. Our Breast Cancer SPORE showed that increased expression of VEGF caused acquired tamoxifen resistance 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 end point 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: We previously reported a planned interim analysis. Results of further analysis after completion of accrual will be reported here. All 27 patients were female with median age of 63 years, and all had ER and/or PR positive MBC. Patients were continued on the same hormonal 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 18 (66%) patients. There were no complete or partial responses. Updated median TTP will be reported. Conclusions: The combination of bevacizumab plus hormonal therapy is well tolerated in patients with metastatic breast cancer. This combination may prolong the TTP with acceptable toxicity. Further investigation utilizing this combination in metastatic breast cancer are ongoing. [Table: see text]