2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial.
BACKGROUND
Trastuzumab--a humanised monoclonal antibody against HER2--has been shown to improve disease-free survival after chemotherapy in women with HER2-positive early breast cancer. We investigated the drug's effect on overall survival after a median follow-up of 2 years in the Herceptin Adjuvant (HERA) study.


METHODS
HERA is an international multicentre randomised trial that compared 1 or 2 years of trastuzumab treatment with observation alone after standard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node positive or high-risk node negative breast cancer. 5102 women participated in the trial; we analysed data from 1703 women who had been randomised for treatment with trastuzumab for 1 year and 1698 women from the control group, with median follow-up of 23.5 months (range 0-48 months). The primary endpoint of the trial was disease-free survival. Here, we assess overall survival, a secondary endpoint. Analyses were done on an intent-to-treat basis. This trial is registered with the European Clinical Trials Database, number 2005-002385-11.


RESULTS
97 (5.7%) patients randomised to observation alone and 58 (3.4%) patients randomised to 1 year of treatment with trastuzumab were lost to follow-up. 172 women stopped trastuzumab prematurely. 59 deaths were reported for trastuzumab and 90 in the control group. The unadjusted hazard ratio (HR) for the risk of death with trastuzumab compared with observation alone was 0.66 (95% CI 0.47-0.91; p=0.0115). 218 disease-free survival events were reported with trastuzumab compared with 321 in the control group. The unadjusted HR for the risk of an event with trastuzumab compared with observation alone was 0.64 (0.54-0.76; p<0.0001).


CONCLUSIONS
Our results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years. The emergence of this benefit after only 2 years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer.
Smith
Ian
I
Royal Marsden Hospital, London, UK. ian.smith@rmh.nhs.uk
Procter
Marion
M
Gelber
Richard D
RD
Guillaume
Sébastien
S
Feyereislova
Andrea
A
Dowsett
Mitch
M
Goldhirsch
Aron
A
Untch
Michael
M
Mariani
Gabriella
G
Baselga
Jose
J
Kaufmann
Manfred
M
Cameron
David
D
Bell
Richard
R
Bergh
Jonas
J
Coleman
Robert
R
Wardley
Andrew
A
Harbeck
Nadia
N
Lopez
Roberto I
RI
Mallmann
Peter
P
Gelmon
Karen
K
Wilcken
Nicholas
N
Wist
Erik
E
Sánchez Rovira
Pedro
P
Piccart-Gebhart
Martine J
MJ
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab