Final results of a phase II study of paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer

• DOI: 10.1007/s12094-014-1210-x
• Publication Date: 2014-08-13T14:59:36Z
• Authors: J. Salvador; L. Manso; J. de la Haba; A. Jaen; E. Ciruelos; M. C. de Villena; M. Gil; A. Murias; A. Galan; C. Jara; J. Bayo; J. M. Baena; J. Casal; J. R. Mel; I. Blancas; P. Sanchez Rvira
• Keywords: Adult; Aged, 80 and over; Paclitaxel; Receptor, ErbB-2; Breast Neoplasms; Middle Aged; Antibodies, Monoclonal, Humanized; Neoplastic Cells, Circulating; Prognosis; Deoxycytidine; Receptor, Angiotensin, Type 1; 3. Good health; Bevacizumab; Survival Rate; Translational Research, Biomedical; 03 medical and health sciences; 0302 clinical medicine; Antineoplastic Combined Chemotherapy Protocols; Humans; Female; Aged; Follow-Up Studies; Neoplasm Staging

Efficacy and safety data for combining bevacizumab, gemcitabine, and paclitaxel for locally advanced/metastatic breast cancer are limited.AVALUZ trial evaluates the combination of bevacizumab 10 mg/kg, gemcitabine 2,000 mg/m(2) plus paclitaxel 150 mg/m(2), on days 1 and 15 of each 28-day course in previously untreated HER-2 negative patients.Median progression-free survival (PES): 12.3 months. The overall response and clinical benefit rate (CR + PR + SD) were 72 % (95 % CI 60.9-82.0 %) and 89 % (95 % CI 80.3-95.3 %), respectively. Median overall survival: 27.4 mo. Baseline circulating tumor cell (CTCs) ≥2 versus CTCs <2 was associated with lower PFS, p = 0.046. Overall response was significantly greater in patients with intense angiotensin type 1 receptor (AGTR1) expression (99 vs. 60 % [p = 0.021]). The most frequent grade 3/4 adverse events were: neutropenia (10 %); febrile neutropenia (1 %); sensory neuropathy (13 %); and asthenia (6 %). Grade 3 adverse events of interest with bevacizumab included bleeding (1 %) and hypertension (4 %). One patient developed cardiac ischemia (1 %).Adding bevacizumab to chemotherapy appeared feasible and well tolerated, producing toxicity comparable to other effective combined first-line regimens. Baseline circulating endothelial cells and AGTR1 expression are predictive of PFS and response.