Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial o

We conducted a phase II study in patients with HER2-positive locally advanced breast cancer or pathologic stage 3 breast cancer. Patients received epirubicin with cyclophosphamide followed by docetaxel. Targeted therapy with trastuzumab and bevacizumab were administered for 1 year. The pathologic complete response was comparable with other chemotherapy regimens and the high recurrence-free survival and overall survival are of interest in these high-risk populations. Background: The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). Patients and Methods: Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m) followed by 4 cycles of docetaxel (100 mg/m). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year. Coprimary end points were (1) rate of cardiac events (CEs) in all patients defined as clinical congestive heart failure with a significant decrease in left ventricular ejection fraction or cardiac deaths; and (2) pathologic complete response (pCR) in breast and nodes in the neoadjuvant cohort. An independent cardiac review panel determined whether criteria Presented in part at the ASCO Breast Cancer Symposium 2009. ClinicalTrials.gov: NCT00464646. National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA Columbia River Oncology Program, Portland, OR International Drug Development Institute, Louvain-la-Neuve, Belgium Department of Medicine, Oncology, University of Pittsburgh Cancer Institute, and Magee-Womens Hospital Womens Cancer Clinic, Pittsburgh, PA Virginia Commonwealth University Massey Cancer Center, Richmond, VA Centre hospitalier de l’Université de Montreal (CHUM), Montréal, Québec, Canada Western Oncology Research Consortium, Portland, OR Community Clinical Oncology Program (CCOP) Northern Indiana Cancer Research Consortium, Mishawaka, IN Southeast Clinical Oncology Research Consortium, Roper St Francis Cancer Care, Charleston, SC Community Clinical Oncology Program (CCOP) Michigan Cancer Research Consortium Community, Ann Arbor, MI Community Clinical Oncology Program (CCOP) Dayton, Dayton, OH Community Clinical Oncology Program (CCOP) Kalamazoo, and the West Michigan Cancer Center, Kalamazoo, MI Kaiser Permanente, San Diego, CA Department of Oncology, UF Cancer Center at Orlando Health, Orlando, FL WashingtonCancer Institute,MedStarWashingtonHospital Center,Washington,DC Georgetown University Medical Center, Washington, DC Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA Submitted: Mar 9, 2016; Revised: Jun 27, 2016; Accepted: Jul 20, 2016; Epub: Jul 28, 2016 Address for correspondence: Priya Rastogi, MD, NSABP Foundation, Inc, Nova Tower Two/Two Allegheny Center e 12th Fl, Ste 1249, Pittsburgh, PA 15212 Fax: 412-697-6623; e-mail contact: [email protected] 48 Clinical Breast Cancer February 2017 1526-8209/$ see frontmatter a 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clbc.2016.07.008 for a CE were met. Results: A total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2 months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall survival (OS) for all patients was 79.9% and 90.8%, respectively. Conclusion: The regimen met predefined criteria for activity of interest with an acceptable rate of CEs. Although the pCR percentage was comparable with chemotherapy regimens with trastuzumab alone the high RFS and OS are of interest in these high-risk populations. Clinical Breast Cancer, Vol. 17, No. 1, 48-54 a 2016 Elsevier Inc. All rights reserved.