Efficacy and safety of the administration of bevacizumab in combination with first-line chemotherapy for the treatment of advanced breast carcinoma: ATHENA MO19391 study results in Spanish patients
© BioMed Central Ltd. 2009
Published: 23 June 2009
Bevacizumab (BVZ) is a humanized monoclonal antibody that targets vascular endothelial growth factor, that leads to the inhibition of growth and proliferation of new blood vessels that are next to the tumor. The administration of BVZ plus first-line chemotherapy (paclitaxel, docetaxel) in the treatment of advanced breast carcinoma has lead to better outcomes in terms of response rate and time to progression in previous published studies.
The ATHENA MO19391 study is a nonrandomized, open-labeled, international trial that tests the addition of BVZ (10 mg/kg/2 weeks or 15 mg/kg/3 week) to first-line chemotherapy (nonanthracycline based) in the treatment of advanced breast cancer. Results of the ATHENA trial have been previously reported. In the global study, 2,027 patients were included in 37 participating countries, between September 2006 and June 2008. This report shows the current efficacy and safety data of ATHENA participating patients included in Spanish centers.
A total of 119 patients in 20 Spanish centers were included in the trial, with the following basal characteristics: median age 51 years (27 to 79); postmenopausal status, 83 patients (69.7%); estrogen receptor-positive, 64 patients (66.7%); HER2-negative, HER2-positive, unknown, 92 patients (95.8%), two patients (2.1%), two patients (2.1%), respectively; prior adjuvant therapy, 92 patients (95.8%) – anthracycline-based, 63 patients (72.4%) and taxane-based, 38 patients (43.6%). The majority of patients (68 patients, 57.1%) who received previous adjuvant treatment had a disease-free interval >24 months.
The most common chemotherapy regimens that were combined with BVZ were paclitaxel (48 patients, 40.3%) and docetaxel (41 patients, 34.5%). Other used regimens were paclitaxel + gemcitabine (six patients, 5%), capecitabine (three patients, 2.5%), and others. The median number of administered cycles per patient was 8 (1 to 27). With a median follow-up of 10.9 months (0.9 to 24.9), 46% of patients had disease progression. The median time to progression was 11.5 months (10 to 13.6), and median overall survival was 22.5 months (19.2 to NR). One hundred and ten patients were evaluable for efficacy. Fourteen patients (12.7%) achieved a complete response, and 60 patients (54.5%) a partial response, for an overall response rate of 67.2%. Twenty-seven patients (24.5%) had stable disease, and nine (8.2%) progressed. The clinical benefit rate was 91.7%. Thirty-one patients (26.1%) had at least one adverse event grade ≥ 3. The most relevant SAEs were: febrile neutropenia, five patients (4.2%); grade 1 to 2 hypertension, 41 patients (34.4%); grade 3 to 4 hypertension, eight patients (6.7%); grade 1 to 2 epistaxis, 60 patients (50.4%); grade 3 DVT, one patient (0.8%); grade 1 to 3 proteinuria, 32 patients (26.9%); grade 4 nephrotic syndrome, two patients (1.7%); grade 3 GI perforation, one patient (0.8%); and grade 1 to 2 impaired healing, four patients (3.4%). Thirty-two patients (26.9%) had died at the time of the analysis, the majority (31 patients) due to breast cancer progression.
Chemotherapy (nonanthracycline based) plus BVZ as first-line treatment for advanced breast cancer has a high antitumor activity in terms of response rate and clinical benefit and of time to progression. The toxicity profile is manageable and due to toxic effects of both treatments separately. Administration of BVZ plus chemotherapy must be considered first-line therapy for the treatment of advanced breast cancer.