SAN ANTONIO – When given along with conventional hormone therapy, bevacizumab improved neither disease-free progression times nor mortality, compared with conventional treatment alone in patients with advanced breast cancer.
The median progression-free survival time for the combination regimen was 18.4 months, compared with 13.8 months for standard estrogen therapy alone – a nonsignificant 17% risk reduction in the phase III LEA trial (hazard ratio, 0.83; P = .14)
© SABCS/Todd Buchanan 2012
Dr. Miguel Martin
Median overall survival was 41 months with bevacizumab (Avastin) added and 42 months with standard therapy (HR, 1.18; P = .469), Dr. Miguel Martin reported at the San Antonio Breast Cancer Symposium. There were 42 deaths in each group.
"Adding bevacizumab to estrogen therapy as a first-line treatment had no impact on progression-free survival or overall survival," said Dr. Martin of the Instituto de Investigación Sanitaria Gregorio Marañón, Madrid.
The phase III LEA (letrozole/fulvestrant and Avastin) trial included 380 patients with unresectable locally advanced or metastatic breast cancer that was hormone receptor–positive and HER2 negative. They were randomized to one of two treatment regimens: conventional hormone therapy of letrozole (Femara, 2.5 mg daily) or fulvestrant (Faslodex, 250 mg monthly) or to one of those drugs with concomitant bevacizumab (15 mg/kg every 3 weeks). Most patients in both trial arms received letrozole (89%-92%).
All of the patients were postmenopausal. Although previous treatment with adjuvant aromatase inhibitors was allowed, the patients had no prior therapy for advanced disease, said Dr. Martin.
The patients’ median age was 65 years (38-86 years). Most (72%) were fully active, with an Eastern Cooperative Oncology Group score of 0. About 80% were metastatic, with 48% having visceral disease and 65% measurable bone lesions.
Almost all patients had received some form of adjuvant therapy, including 44% who had undergone adjuvant chemotherapy and 51% who had taken adjuvant endocrine therapy.
Anemia occurred in virtually all patients, but neutropenia was seen in just 6% of the standard therapy group and 11% of the combination group – not a significant difference. Both leukopenia and thrombocytopenia were significantly more common in the combination group (leukopenia, 25% vs. 11%; P = less than .001; and thrombocytopenia 19% vs. 9%; P = .006).
Nonhematologic toxicities were significantly more common among patients taking the combination treatment. Fatigue was present in 51% of the combination group vs. 29% of the standard therapy group, hypertension in 59% vs. 16%, hemorrhage in 19% vs. 2%, liver enzyme elevation in 47% vs. 28%, and proteinuria in 30% vs. 3%, respectively. All of these differences were highly significant statistically (P less than .001).
There was no significant between-group difference in the occurrence of thromboembolic events (2% vs. 0%; P = .373).
Dr. Martin said that the control group did much better than was expected. However, he suggested that biomarker studies might be able to pinpoint a select population that could benefit from the addition of bevacizumab to standard hormonal therapy.
Dr. Martin is on the speakers bureau and a consultant for Roche.