Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1): a multicentre, single-arm, phase 2 study

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• 作者：Prof Franç ; ois Bertucci ; MD^a ; ^b ; ^{bertuccif@ipc.unicancer.fr" class="auth_mail" title="E-mail the corresponding author} ; Mahmoud Fekih ; MD^c ; Auré ; lie Autret ; MSc^a ; Prof Thierry Petit ; MD^d ; Florence Dalenc ; MD^e ; Christelle Levy ; MD^f ; Gilles Romieu ; MD^g ; Prof Jacques Bonneterre ; MD^h ; Prof Jean-Marc Ferrero ; MDⁱ ; Prof Pierre Kerbrat ; MD^j ; Patrick Soulie ; MD^k ; Marie-Ange Mouret-Reynier ; MD^l ; Thomas Bachelot ; MD^m ; Florence Lerebours ; MDⁿ ; Jean-Christophe Eymard ; MD^o ; Mathilde Deblock ; MD^p ; Alain Lortholary ; MD^q ; Anne-Claire Hardy-Bessard ; MD^r ; Philippe Barthelemy ; MD^s ; Prof Hervé ; Bonnefoi ; MD^t ; Prof Emmanuelle Charafe-Jauffret ; MD^a ; ^b ; Franç ; ois-Clé ; ment Bidard ; MD^u ; Prof Patrice Viens ; MD^a ; ^b ; Jé ; rô ; me Lemonnier ; PhD^v ; Prof Jean-Yves Pierga ; MD^u ; ^w
• 刊名：The Lancet Oncology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：17
• 期：5
• 页码：600-611
• 全文大小：376 K

文摘

Addition of bevacizumab to standard chemotherapy in the neoadjuvant setting in patients with HER2-negative metastatic breast cancer improves progression-free survival and the proportion of patients achieving pathological complete response. In the BEVERLY-1 (UCBG-0802) trial we aimed to assess the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy in the treatment of patients with HER2-negative inflammatory breast cancer.

Methods

We did this phase 2, single-arm trial at 20 hospitals in France. We enrolled women aged 18 years or older who had non-metastatic HER2-negative inflammatory breast cancer. Patients underwent 3-week treatment cycles, receiving neoadjuvant intravenous fluorouracil (500 mg/m²), epirubicin (100 mg/m²), cyclophosphamide (500 mg/m²), and bevacizumab (15 mg/kg) during cycles 1–4, then docetaxel (100 mg/m²) and bevacizumab during cycles 5–8. 2–4 weeks after surgery, patients received adjuvant radiotherapy, hormone therapy (if they had a hormone receptor-positive tumour), and adjuvant intravenous bevacizumab. The primary endpoint was pathological complete response in breast and axillary lymph nodes after neoadjuvant treatment, determined after centralised review in accordance with Sataloff classification and assessed in the intention-to-treat population. Our analysis of toxic effects included all patients who received at least one dose of bevacizumab. The trial is complete and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT00820547.

Findings

Between Jan 16, 2009, and Sept 8, 2010, we enrolled 101 patients, one of whom withdrew consent before treatment, leaving 100 patients in the primary endpoint analysis. After neoadjuvant therapy, 19 (19% [95% CI 12–28]; p=0·16) of 100 patients achieved a pathological complete response according to centralised review. The most frequent grade 3–4 events during the neoadjuvant phase were neutropenia (89 [89%] of 100 patients), febrile neutropenia (37 [37%]), and mucositis (23 [23%]) and during the adjuvant phase the most frequent grade 3–4 adverse event was proteinuria (5 [7%] of 75 patients). One (1%) patient died of thrombotic microangiopathy after cycle 1, which was thought to be related to bevacizumab. Two patients (3%) developed transitory heart failure. 48 (48%) patients had serious adverse events, the most frequent of which was febrile neutropenia (28 [28%]).

Interpretation

Our results suggest that the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy does not provide clinical benefit to patients with non-metastatic HER2-negative inflammatory breast cancer. Longer follow-up and correlative studies to identify patients who might benefit from bevacizumab are needed.

Funding

Roche, La Ligue Nationale contre le Cancer, UNICANCER, and Chugai Pharma.