Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.
BACKGROUND
We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer.


METHODS
The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel (group 2). The North Central Cancer Treatment Group trial N9831 compared three regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel (group A), the same regimen followed by 52 weeks of trastuzumab after paclitaxel (group B), and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel (group C). The studies were amended to include a joint analysis comparing groups 1 and A (the control group) with groups 2 and C (the trastuzumab group). Group B was excluded because trastuzumab was not given concurrently with paclitaxel.


RESULTS
By March 15, 2005, 394 events (recurrent, second primary cancer, or death before recurrence) had been reported, triggering the first scheduled interim analysis. Of these, 133 were in the trastuzumab group and 261 in the control group (hazard ratio, 0.48; P<0.0001). This result crossed the early stopping boundary. The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years. Trastuzumab therapy was associated with a 33 percent reduction in the risk of death (P=0.015). The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831.


CONCLUSIONS
Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer. (ClinicalTrials.gov numbers, NCT00004067 and NCT00005970.)
Romond
Edward H
EH
National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, USA.
Perez
Edith A
EA
Bryant
John
J
Suman
Vera J
VJ
Geyer
Charles E
CE
Davidson
Nancy E
NE
Tan-Chiu
Elizabeth
E
Martino
Silvana
S
Paik
Soonmyung
S
Kaufman
Peter A
PA
Swain
Sandra M
SM
Pisansky
Thomas M
TM
Fehrenbacher
Louis
L
Kutteh
Leila A
LA
Vogel
Victor G
VG
Visscher
Daniel W
DW
Yothers
Greg
G
Jenkins
Robert B
RB
Brown
Ann M
AM
Dakhil
Shaker R
SR
Mamounas
Eleftherios P
EP
Lingle
Wilma L
WL
Klein
Pamela M
PM
Ingle
James N
JN
Wolmark
Norman
N
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012008:Recurrence; D016019:Survival Analysis; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D004317:Doxorubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C010013:adriamycinol