First-line treatment with endocrine therapy plus bevacizumab did not significantly improve PFS compared with endocrine therapy alone for postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer, according to results from a multicenter phase III trial published online Feb. 17 in Journal of Clinical Oncology.

Furthermore, patients taking endocrine therapy plus bevacizumab (ET-B) had significantly more adverse events.

“On the basis of this particular trial and in light of the higher toxicity, ET-B should not be recommended in the treatment of advanced hormone receptor-positive/HER2-negative breast cancer,” wrote Dr. Miguel Martín of Universidad Complutense de Madrid and his associates (J. Clin. Oncol. 2015 Feb. 17 [doi:10.1200/JCO.2014.57.2388] ).

Previous studies have shown overexpression of VEGF in breast cancer and that high VEGF levels are associated with early recurrence and resistance to hormone therapy. The Letrozole/Fulvestrant and Avastin (LEA) Study evaluated whether anti-VEGF bevacizumab in combination with ET would improve outcomes. After a median follow up of 23.7 months, patients in the ET-B arm had a median PFS of 19.3 months (95% CI, 16.5-22.1) vs. 14.4 months (11.4-17.5) for patients taking ET alone (P = .125). Compared with the ET alone arm, patients in the ET-B arm had improved ORR (40.8% vs 21.9%, P < .001) and CBR (76.8% vs 67.4%, P = .041). Grade 3-4 adverse events were significantly more frequent in the ET-B arm, including hypertension (15.0% vs 3.0%, P < .001), aminotransferase elevation (3.7% vs 1.0%, P = .068), and proteinuria (7.0% vs 0.0%, P < .001). In the ET-B arm, 39 patients (20.5%) discontinued treatment, including 8 patients who died. There were no toxicity-related deaths in the ET arm.

“Although the potential impact of age and comorbidities should not be discounted in the mortality outcomes of the LEA study, we observed an unexpectedly high rate of toxicity-related deaths among patients receiving ET-B. In addition, adverse events were significantly higher in the ET-B arm. Therefore, a toxicity interaction between these agents cannot be ruled out and should be carefully monitored in ongoing studies with this combination,” wrote Dr. Martin and colleagues.