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 of the NSABP Foundation Research Group, FB-5.
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 received every 3 week treatment with 4 cycles of EC (90/600 mg/m2) followed by 4 cycles of docetaxel (100 mg/m2). 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 for a CE were met.



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.



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.
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Columbia River Oncology Program, Portland, OR.
John W
JW
Smith
International Drug Development Institute, Louvain-la-Neuve, Belgium.
Marc E
ME
Buyse
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Department of Medicine, Oncology, University of Pittsburgh Cancer Institute, and Magee-Womens Hospital Womens Cancer Clinic, Pittsburgh, PA. Electronic address: rastogip@upmc.edu.
Priya
P
Rastogi
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Virginia Commonwealth University Massey Cancer Center, Richmond, VA.
Charles E
CE
Geyer
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Department of Medicine, Oncology, University of Pittsburgh Cancer Institute, and Magee-Womens Hospital Womens Cancer Clinic, Pittsburgh, PA.
Samuel A
SA
Jacobs
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Centre hospitalier de l'Université de Montreal (CHUM), Montréal, Québec, Canada.
Erica J
EJ
Patocskai
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Centre hospitalier de l'Université de Montreal (CHUM), Montréal, Québec, Canada.
André
A
Robidoux
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Western Oncology Research Consortium, Portland, OR.
Alison K
AK
Conlin
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Community Clinical Oncology Program (CCOP) Northern Indiana Cancer Research Consortium, Mishawaka, IN.
Bilal
B
Ansari
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Southeast Clinical Oncology Research Consortium, Roper St Francis Cancer Care, Charleston, SC.
George P
GP
Keogh
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Community Clinical Oncology Program (CCOP) Michigan Cancer Research Consortium Community, Ann Arbor, MI.
Philip J
PJ
Stella
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Community Clinical Oncology Program (CCOP) Dayton, Dayton, OH.
Howard M
HM
Gross
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Community Clinical Oncology Program (CCOP) Kalamazoo, and the West Michigan Cancer Center, Kalamazoo, MI.
Raymond S
RS
Lord
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Kaiser Permanente, San Diego, CA.
Jonathan A
JA
Polikoff
International Drug Development Institute, Louvain-la-Neuve, Belgium.
Celine
C
Mauquoi
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Department of Oncology, UF Cancer Center at Orlando Health, Orlando, FL.
Eleftherios P
EP
Mamounas
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Washington Cancer Institute, MedStar Washington Hospital Center, Washington, DC; Georgetown University Medical Center, Washington, DC.
Sandra M
SM
Swain
National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA.
Norman
N
Wolmark
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab / Q000008:administration & dosage
D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human
Neoadjuvant chemotherapy