Efficacy results from a multicenter phase II noncomparative two-arm pilot trial of bevacizumab with anastrozole or fulvestrant as first-line endocrine therapy for metastatic breast cancer

Abstract

1091 Background: Estrogen modulates angiogenesis via effects on endothelial cells with subsequent induction of vascular endothelial growth factor (VEGF). VEGF promotes tumor growth and is associated with poor response to antiestrogen therapy. This trial was designed to evaluate the progression-free survival (PFS) of bevacizumab (B) in combination with anastrozole (A) or fulvestrant (F) as first-line endocrine therapy (ET) in metastatic breast cancer (MBC). Methods: Eligibility criteria: no prior hormonal or chemotherapy for MBC, measurable or evaluable disease, normal LVEF, post-menopausal. Treatment: Arm A: anastrozole 1 mg po QD in pts who were a) ET naïve, b) ≥ 12 months from adjuvant ET, and c) intolerant of or progressed on prior tamoxifen. Arm B: fulvestrant 500 mg D1 and 250 mg D15 IM loading dose followed by 250 mg q28 days in pts who were a) < 12 months from adjuvant aromatase inhibitors (AIs), b) intolerant of or progressed on AIs, and c) MD's discretion. Bevacizumab 10 mg/kg IV D1 q2 weeks was given in both arms. Trastuzumab permitted in HER-2+ pts only. Response assessments were q8 weeks; pts were treated until disease progression or toxicity. Results: 79 pts were enrolled fromNovember 2006 to November 2008. 42 pts are evaluable for response and toxicity, Arm A - 25 pts and Arm B - 17 pts. Median age was 64, ECOG PS 0 - 55%, 1- 43 %, adjuvant chemo 27%, adjuvant hormonal -38%, hormone receptor status: ER+/PR+ 80%, ER+/PR- 14%, ER-/PR+ 2 %. HER-2+ 5 pts, 31% had ≥ 2 metastatic disease sites predominately lung and bone only disease - 40%. Median # cycles - 4. 24% achieved a partial response and 57% stable disease; 7 pts progressed. G3 hypertension (12%) was the most common toxicity. Median PFS for Arm A was 16.3 months and has not yet been reached for Arm B. Conclusions: Bevacizumab in combination with anastrozole or fulvestrant is feasible and well tolerated with no unanticipated toxicities. The addition of bevacizumab resulted in prolongation of the median PFS to16.3 months with anastrozole as compared to the 7–9 month historical control PFS reported for first-line AI monotherapy in MBC. Further evaluation of bevacizumab endocrine combinations is warranted. [Table: see text]

Antiangiogenic therapy for breast cancer

“…A phase II trial of bevacizumab plus letrozole in 32 postmenopausal women with hormone-receptor-positive advanced breast cancer (ABC) revealed 2 patients with PR and 13 with SD for 6 months or more [ 27 ]. Preliminary results from a two arm noncomparative phase II study of bevacizumab combined with anastrozole (25 patients) or fulvestrant (17 patients) as first-line therapy in MBC reported promising results with a PR rate of 24%, a SD rate of 57%, a median PFS of 16.3 months for the anastrozole arm, and median PFS not reached in the fulvestrant arm [ 28 ]. A similar phase II study of bevacizumab plus fulvestrant in 33 MBC patients previously treated with an aromatase inhibitor did not meet its statistical endpoint, as only 22% (11% PR + 11% SD ≥6 months) of the patients achieved clinical benefit with a median PFS of 6.2 months [ 29 ].…”