Practice Update: Oncology

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Adjuvant Tamoxifen and
Exemestane inWomen
With Postmenopausal Early
Breast Cancer
The Lancet Oncology
Take-home message
• This extended follow-up of a phase III trial was designed to assess outcomes
with different hormone therapy combinations in postmenopausal patients with
early-stage, hormone receptor–positive breast cancer. Patients were randomized to
either 5 years of exemestane monotherapy or to a sequential scheme of tamoxifen
for 2.5 to 3.0 years followed by exemestane, for a total duration of 5 years. After a
median follow-up of 9.8 years, disease-free survival was similar between the groups.
• These results suggest that both approaches are reasonable for adjuvant endocrine
therapy in postmenopausal women.
Abstract
BACKGROUND After 5 years of median follow-up,
the Tamoxifen Exemestane Adjuvant Multina-
tional (TEAM) trial reported no difference in
disease-free survival between exemestane
monotherapy and a sequential scheme of
tamoxifen followed by exemestane in post-
menopausal patients with early-stage, hormone
receptor-positive breast cancer. As recurrence
risk in hormone receptor-positive breast cancer
remains linear beyond 5 years after diagnosis,
we analysed long-term follow-up outcomes of
this trial.
METHODS The TEAM trial, a multicentre, open-la-
bel, randomised, controlled, phase 3 trial,
included postmenopausal patients with ear-
ly-stage hormone receptor-positive breast
cancer from nine countries. Patients were
randomly allocated (1:1) by a computer-gener-
ated random permuted block method (block
sizes 4-8) to either 5 years of oral exemestane
monotherapy (25 mg once a day) or a sequen-
tial scheme of oral tamoxifen (20 mg once a
day) followed by exemestane for a total dura-
tion of 5 years. After the publication of the IES
trial, the protocol was amended (Dec 13, 2004).
Patients assigned to tamoxifen were switched
after 2•5-3•0 years to exemestane therapy for
a total duration of 5•0 years of treatment. Ran-
domisation was done centrally in each country.
Long-term follow-up data for disease recurrence
and survival was collected in six participating
countries and analysed by intention to treat. The
primary endpoint was disease-free survival at 10
years of follow-up.
FINDINGS 6120 patients of the original 9776
patients in the TEAM trial were included in
the current intention-to-treat analysis. Median
follow-up was 9•8 years (IQR 8•0-10•3). Dur-
ing follow-up, 921 (30%) of 3075 patients in
the exemestane group and 929 (31%) of 3045
patients in the sequential group had a dis-
ease-free survival event. Disease-free survival at
10 years was 67% (95% CI 65-69) for the exemes-
tane group and 67% (65-69) for the sequential
group (hazard ratio 0•96, 0•88-1•05; p=0•39).
INTERPRETATION The long-term findings of the
TEAM trial confirm that both exemestane alone
and sequential treatment with tamoxifen fol-
lowed by exemestane are reasonable options
as adjuvant endocrine therapy in postmeno-
pausal patients with hormone receptor-positive
early breast cancer. These results suggest that
the opportunity to individualise adjuvant endo-
crine strategy accordingly, based on patient
preferences, comorbidities, and tolerability
might be possible.
Adjuvant tamoxifen and exemestane in women
with postmenopausal early breast cancer
(TEAM): 10-year follow-up of a multicentre,
open-label, randomised, phase 3 trial. Lancet
Oncol 2017 Jul 18;[EPub Ahead of Print], MGM
Derks, EJ Blok, C Seynaeve, et al.
COMMENT
By Annette Hasenburg Prof. Dr. med
L ong-term findings of the TEAM
study – a randomized, open-label
phase III trial comparing 5 years of
exemestane with 2 to 3 years of tamox-
ifen followed by exemestane as adjuvant
therapy for postmenopausal patients with
hormone receptor (HR)-positive breast
cancer – are presented in the July 2017
issue of The Lancet Oncology.
After a median follow-up of 9.8 years
of 6120 patients in 9 countries, 10-year
disease-free survival was 67% in both
arms. Even patients with low-risk tumors
continued to relapse over time despite
endocrine therapy.
Breast cancer recurrence was lower in the
exemestane group (20%; 95% CI, 19–22)
than in the sequential arm (22%; sub-dis-
tribution HR for recurrence-free interval
0.88, 95% CI 0.79–0.99), but other-cause
mortality was higher with exemestane.
There seems to be a trade-off between
toxic effects and efficacy, resulting in sim-
ilar overall survival in both arms.
There was no identification of any clin-
icopathological subgroup that showed a
benefit from either strategy. Hope for the
future is to find biomarkers that will allow
a better stratification of patients.
Both strategies are reasonable options for
postmenopausal women with HR-positive
breast cancer, and should be selected
according to the patient’s risk profile and
the possible side effects.
Two questions will still have to be
answered: 1) optimum length of treatment
and 2) combination of antihormonal drugs
with other components to overcome
endocrine resistance (eg, CDK 4–6 inhib-
itors).
Dr Hasenburg is Director of
Obstetrics and Gynecology
Mainz University Medical
Center, Mainz, Germany.
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PRACTICEUPDATE ONCOLOGY