Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.
BACKGROUND
Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival.


METHODS
4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920.


RESULTS
After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded.


CONCLUSIONS
Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.
Coombes
R C
RC
Cancer Research UK Department of Cancer Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Imperial College London, Faculty of Medicine, Hammersmith Hospitals Trust, London W12 0NN, UK.
Kilburn
L S
LS
Snowdon
C F
CF
Paridaens
R
R
Coleman
R E
RE
Jones
S E
SE
Jassem
J
J
Van de Velde
C J H
CJ
Delozier
T
T
Alvarez
I
I
Del Mastro
L
L
Ortmann
O
O
Diedrich
K
K
Coates
A S
AS
Bajetta
E
E
Holmberg
S B
SB
Dodwell
D
D
Mickiewicz
E
E
Andersen
J
J
Lønning
P E
PE
Cocconi
G
G
Forbes
J
J
Castiglione
M
M
Stuart
N
N
Stewart
A
A
Fallowfield
L J
LJ
Bertelli
G
G
Hall
E
E
Bogle
R G
RG
Carpentieri
M
M
Colajori
E
E
Subar
M
M
Ireland
E
E
Bliss
J M
JM
D000368:Aged; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017698:Postmenopause; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*
D000730:Androstadienes; D047072:Aromatase Inhibitors; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C056516:exemestane