NO PFS BENEFIT OF BEVACIZUMAB IN HR+ BREAST CANCER

In a Spanish-German phase III LEA trial reported in the Journal of Clinical Oncology, Martín et al found that adding bevacizumab (Avastin) to endocrine therapy with letrozole or fulvestrant (Faslodex) in the first-line treatment of postmenopausal women with advanced breast cancer did not improve progression-free or overall survival.

Study Details

In this open-label trial, 374 women with HER2-negative, hormone receptor–positive advanced disease were randomly assigned between November 2007 and August 2011 to receive bevacizumab 15 mg/kg every 3 weeks plus endocrine therapy (n = 190) or endocrine therapy alone (n = 184). All patients received letrozole except for 16 in the bevacizumab group and 21 in the control group. The primary endpoint was progression-free survival.

The bevacizumab and control groups were generally balanced for age (median 64 and 66 years, 47% and 54% ≥ 65 years), country (Spain for 71% in both), Eastern Cooperative Group performance status (0 for 73% and 71%, 1 for 27% and 29%), median disease-free interval (4.3 years in both), prior (neo)adjuvant chemotherapy (44% and 48%, taxanes or anthracyclines in 34% and 36%), prior (neo)adjuvant endocrine therapy (53% and 52%, antiestrogens in 34% and 32%), disease stage (metastatic in 97% in both), at least two metastatic sites (58% and 64%), visceral disease (47% and 48%, lung in 33% and 37%), and measurable disease (75% and 79%).

Progression-Free Survival

The median duration of treatment was 13.8 months in the bevacizumab group and 14.0 months in the control group. The median follow-up was 23.7 months. Median progression-free survival was 19.3 months in the bevacizumab group vs 14.4 months in the control group (hazard ratio [HR] = 0.83, P =.126). On multivariate analysis, prior (neo)adjuvant endocrine therapy (P = .011) and type of endocrine therapy received during the study (P = .015) were independent predictors of progression-free survival.

The overall response rate was 41% vs 22% (P < .001), clinical benefit rate was 77% vs 67% (P = .041), and median response duration was 17.6 vs 13.3 months (P = .434). Median time to treatment failure was 15.1 vs 14.4 months. Median overall survival was 52.1 vs 51.8 months (HR = 0.87, P = .518).

Adverse Events

Grade 3 or 4 hypertension (15% vs 3%) and proteinuria (7% vs 0%) were significantly more common (P < .001) in the bevacizumab group. Serious adverse events occurred in 25% vs 9% of patients (P < .05). Thromboembolic events occurred in four patients vs one patient. Eight  patients in the bevacizumab group (4.2%) vs none in the control group died from adverse events, including pulmonary embolism in one, heart failure in one, cerebellum infarction in one, liver failure in one, and acute myocardial infarction in two.

The investigators concluded: “The addition of bevacizumab to [endocrine therapy] in first-line treatment failed to produce a statistically significant increase in [progression-free survival] or [overall survival] in women with HER2-negative/hormone receptor–positive advanced breast cancer.”

Miguel Martín, MD, PhD, of Universidad Complutense de Madrid, is the corresponding author of the Journal of Clinical Oncology article.

The study was supported by F. Hoffmann-La Roche. For full disclosures of the study authors, visit jco.ascopubs.org.