Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study.

BACKGROUND: Bevacizumab and trastuzumab are efficacious for treatment of advanced or HER2-positive metastatic breast cancer; however, few data exist for this regimen in inflammatory breast cancer. In our phase 2 trial, we aimed to assess efficacy and safety of neoadjuvant bevacizumab combined with trastuzumab and chemotherapy in patients with primary HER2-positive inflammatory breast cancer.

METHODS: In our phase 2, multicentre, open-label, single-arm, non-comparative trial, we enrolled women (aged ≥ 18 years) with histologically confirmed HER2-positive non-metastatic inflammatory breast cancer at private or public oncology centres in France. Before surgery, patients were treated with fluorouracil, epirubicin, cyclophosphamide, and bevacizumab (cycles 1-4) and docetaxel, bevacizumab, and trastuzumab (cycles 5-8) in 3-week cycles. After surgery, patients received adjuvant radiotherapy, trastuzumab, and bevacizumab. For the primary endpoint, we assessed the proportion of patients who achieved a pathological complete response (defined by central review of surgical specimens according to Sataloff classification, counting missing data as failure) and adverse events in all enrolled patients. This study is registered with ClinicalTrials.gov, number NCT00717405.

FINDINGS: Between Oct 23, 2008, and Oct 28, 2009, we enrolled 52 patients at 21 centres. 42 (81%) of 52 patients received all eight cycles of neoadjuvant therapy and 49 (94%) underwent surgery. After neoadjuvant therapy, 33 of 52 patients had a pathological complete response according to central review (63·5%, 95% CI 49·4-77·5). The most common adverse events were asthenia and nausea (both occurred in 36 [69%] of 52 patients). 25 (48%) patients had grade 3-4 neutropenia, which was the most common grade 3-4 adverse event. Only one grade 3 or worse adverse event regarded as related to bevacizumab was reported (hypertension, one patient). Four patients (8%) had cardiac failure.

INTERPRETATION: Neoadjuvant treatment with bevacizumab, trastuzumab, and chemotherapy was efficacious and well tolerated in patients with previously untreated primary inflammatory breast cancer. Further confirmation of use of bevacizumab in inflammatory breast cancer is needed.

FUNDING: Roche (France).