Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial.
BACKGROUND
Trastuzumab (Herceptin(R)) improves disease-free survival (DFS) and overall survival for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess the magnitude of its clinical benefit for subpopulations defined by nodal and steroid hormone receptor status using data from the Herceptin Adjuvant (HERA) study.


METHODS
HERA is an international multicenter randomized trial comparing 1 or 2 years of trastuzumab treatment with observation after standard chemotherapy in women with HER2-positive breast cancer. In total, 1703 women randomized to 1-year trastuzumab and 1698 women randomized to observation were included in these analyses. Median follow-up was 23.5 months. The primary endpoint was DFS.


RESULTS
The overall hazard ratio (HR) for trastuzumab versus observation was 0.64 [95% confidence interval (CI) 0.54-0.76; P < 0.0001], ranging from 0.46 to 0.82 for subgroups. Estimated improvement in 3-year DFS in subgroups ranged from +11.3% to +0.6%. Patients with the best prognosis (those with node-negative disease and tumors 1.1-2.0 cm) had benefit similar to the overall cohort (HR 0.53, 95% CI 0.26-1.07; 3-year DFS improvement +4.6%, 95% CI -4.0% to 13.2%).


CONCLUSIONS
Adjuvant trastuzumab therapy reduces the risk of relapse similarly across subgroups defined by nodal status and steroid hormone receptor status, even those at relatively low risk for relapse.
Untch
M
M
Helios Klinikum Berlin Buch, Academic Hospital of the University Charite Berlin, Berlin, Germany.
Gelber
R D
RD
Jackisch
C
C
Procter
M
M
Baselga
J
J
Bell
R
R
Cameron
D
D
Bari
M
M
Smith
I
I
Leyland-Jones
B
B
de Azambuja
E
E
Wermuth
P
P
Khasanov
R
R
Feng-Yi
F
F
Constantin
C
C
Mayordomo
J I
JI
Su
C-H
CH
Yu
S-Y
SY
Lluch
A
A
Senkus-Konefka
E
E
Price
C
C
Haslbauer
F
F
Suarez Sahui
T
T
Srimuninnimit
V
V
Colleoni
M
M
Coates
A S
AS
Piccart-Gebhart
M J
MJ
Goldhirsch
A
A
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D038622:Internationality; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016019:Survival Analysis; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab