Transcript ABCSG6a slides

Extended adjuvant treatment
with anastrozole: results from
the ABCSG Trial 6a
R Jakesz, H Samonigg, R Greil,
M Gnant, M Schmid, W Kwasny, E
Kubista, B Mlineritsch, C Tausch, &
M Stierer on behalf of the ABCSG
Introduction
 Adjuvant treatment for early breast cancer with tamoxifen
is limited to 5 years’ duration because of the risks
associated with long-term tamoxifen therapy
 Aromatase inhibitors (AIs) have been investigated in the
extended adjuvant role following 5 years’ adjuvant
tamoxifen therapy and have proven beneficial in reducing
recurrences1
 Anastrozole has shown efficacy and tolerability benefits
over tamoxifen in both the adjuvant and switched-adjuvant
settings but has yet to be investigated as extended
adjuvant therapy
 ABCSG Trial 6a aims to investigate the efficacy and
tolerability of anastrozole in the extended adjuvant role
following 5 years’ adjuvant treatment with tamoxifen
1Goss
PE et al. NEJM 2003; 349: 1793-1802
Methods
 ABCSG Trial 6a is a continuation of ABCSG Trial
6, and investigates the efficacy of anastrozole in
the extended adjuvant setting, following 5 years’
treatment with tamoxifen
 856 postmenopausal women (median age
68.1 years) with hormone-sensitive early breast
cancer who had completed adjuvant treatment
were randomized to receive either anastrozole or
no further treatment for 3 years
 Endpoints included recurrence-free survival and
the incidence of adverse events
ABCSG Trial 6a schema
ABCSG Trial 6a
R
A
N
ABCSG Trial 6
D
Tamoxifen +/aminoglutethemide
5 years
(n=856)
O
Anastrozole 3 years
(n=387)
M
I
Z
E
No treatment 3 years
(n=469)
Disease characteristics of re-randomized patients
Characteristic
Nodal involvement
0 nodes
Anastrozole group
(n, %)
No treatment group
(n, %)
255 (65.9)
323 (68.9)
1-3 nodes
104 (26.8)
112 (23.9)
>3 nodes
28 (7.3)
34 (7.3)
Tumor grade
G1
60 (15.5)
86 (18.3)
G2
220 (56.9)
256 (54.6)
G3
79 (20.4)
92 (19.6)
Gx
28 (7.2)
35 (7.5)
362 (93.5)
447 (95.3)
Negative
10 (2.6)
9 (2.0)
Unknown
15 (3.9)
13 (2.8)
Progesterone receptor status
Positive
319 (82.4)
367 (78.3)
Negative
52 (13.5)
88 (18.8)
Unknown
16 (4.1)
14 (3.0)
Estrogen receptor status
Positive
Incidence of disease recurrence in
ABCSG Trial 6a
Recurrence event
Anastrozole group No treatment group
Total
(n=387)
(n=469)
(n=856)
Loco-regional
10
15
25
Distant metastatic
16
35
51
6
10
16
Total*
30
56
86
Other secondary tumors
18
23
41
Contralateral
*First events only
Results
 Median follow-up was 60 months; all
patients had completed treatment at the
time of analysis
 Risk of recurrence (local, contralateral or
distant metastases) was reduced by 36%
for patients receiving anastrozole
compared with no treatment
– HR = 0.64 (95% CI 0.412, 0.999); p=0.0477
 There was no significant difference
between groups for overall survival
Recurrence-free survival for loco-regional,
contralateral and distant metastatic disease
Recurrence- 100
free
patients
(%)
75
HR 0.64
p=0.0477
50
25
Anastrozole
No treatment
0
0
12
24 36
48
60
Time (months)
72
84
Adverse events
 Analysis of AE data for ABCSG Trial 6a
has yet to be completed
 No problems are anticipated with
anastrozole treatment outside of its
known safety profile
 Mature safety data from the ATAC trial
have already demonstrated a good
tolerability and safety profile for
anastrozole in patients with early disease1
1ATAC
Trialists’ Group. Lancet 2005; 365: 60-62
Discussion (1)
 ABCSG Trial 6a provides more mature follow-up
data for an AI in the extended adjuvant setting
compared with MA 17
 Extended adjuvant therapy with an AI
significantly reduces the risk of recurrence
compared with no further treatment/placebo
– by 36% with 3 years’ anastrozole (median follow-up of
60 months)
– by 43% with 5 years’ letrozole (median follow-up of
29 months)1
1Goss
PE et al. NEJM 2003; 349: 1793-1802
Discussion (2)
 The decrease in recurrence risk achieved with
anastrozole compares well with that of letrozole
considering the differences in patient
populations and lengths of treatment and followup between these trials
 In breast cancer therapy, ASCO currently
recommends the use of the AI “that has been
studied in the setting most closely approximating
any individual patient’s clinical circumstance”1
1Winer
EP et al. J Clin Oncol 2005; 23: 619-629
Conclusion
 Anastrozole is an effective extended
adjuvant therapy that significantly
reduces the risk of recurrence
following 5 years’ treatment with
tamoxifen