Benefits of switching postmenopausal women with hormone-sensitive early breast cancer to anastrozole after 2 years adjuvant tamoxifen: Combined results from 3,224 women enrolled in the ABCSG Trial 8 and the ARNO 95
trial
To prospectively assess whether switching postmenopausal women with hormone receptor-positive early breast cancer from adjuvant tamoxifen (TAM) to anastrozole (ANA) at 2 years is more effective than continuing on adjuvant TAM
Objectives of the combined analysis of ABCSG Trial 8 and the German ARNO 95 trial
Trial endpoints
Primary endpoint
• Event-free survival (EFS)
Secondary endpoints include
• Distant recurrence-free survival (DRFS)
• Tolerability
Events = locoregional recurrences, distant metastases, contralateral breast cancer
Primarysurgery+/- RTx
TAM 3 yearsn=1,606
Total patientsn=3,224
ABCSG 8n=2,262
+ARNO 95
n=962
ANA 3 yearsn=1,618
+ TAM 2 years
ABCSG 8 – ARNO 95:Combined analysis trial structure
Event-free survival:28 months median follow-up
Number Events 3yrs EFS
n=3,224 n=177
TAM 1,606 110 92.7%
ANA 1,618 67 95.8%
Events = locoregional recurrences, distant metastases, contralateral breast cancer
Event-free survival
*Zero point = 2 years after surgery
0
75
80
85
90
95
100
0 1 2 3 4 5
Event-free survival (%)
ANA vs TAM p=0.0009 HR 0.60 [95% CI 0.44-0.81]
EFS time in years*
ANA
TAM
At risk:1606 343 176TAM
ANA 161812171243
858874
593623 375 178
Distant recurrence-free survival
*Zero point = 2 years after surgery
ANADistant recurrence-free survival (%)
TAM
ANA vs TAMp=0.0067 HR 0.61 [95% CI 0.42-0.87]
DRFS time in years
84
88
92
96
100
0 1 2 3 4 5
0
ANA vs TAMp=0.0067
At risk:1606 351 181TAM
ANA 161812241247
869879
600631 382 181
Subgroup analysis of EFS
All patients
Receptor (ER / PR) +ve / +ve
+ve / -ve
Nodal status -ve+ve
Grading G1, G2, GxG3
Age <60 years60 years
0.25
0.50
0.80
1.00
1.25
1.50
2.00
3.00
Hazard ratio (ANA vs TAM)
n
3,224
2,389
833
3,044
167
1,265
1,959
2,519
564
ANA better TAM better
Number Deaths 3 yrs. OS
(%)
TAM 1,606 59 96.4
ANA 1,618 45 97.1
ANA vs TAM p=0.16 HR 0.76 95% CI 0.52-1.12
Overall survival
Tolerability data from ABCSG 8
Both treatments were well tolerated
The incidence of prespecified side effects was low in both groups
As expected, there were significantly more fractures in patients switching to anastrozole: 27 (2.4%) vs 14 (1.2%) for tamoxifen
No significant difference between treatments was seen in gynaecological side effects because - as seen in ATAC - these generally occur soon after starting tamoxifen
Switching from TAM to ANA at 2 years is superior to continuing on TAM in terms of:
• EFS (HR=0.60)
• DRFS (HR=0.61)
The benefits of switching to ANA are seen regardless of baseline prognostic factors
ANA is more effective in G1/G2 tumors
Both treatments are well tolerated
Summary
We now know that ANA is superior to TAM when used as:
• Initial adjuvant therapy for 5 years
and
• When patients are switched from TAM
Trials are needed to determine if one of these approaches is more appropriate than the other
Main question for the future
Postmenopausal women currently on adjuvant tamoxifen
should be switched to anastrozole
after 2 years of treatment
Conclusion
Back up slides
TAM ANA
n=1,606 n=1,618
% %
T1 69.7 70.2
Node negative 74.0 74.2
Breast conservation 77.3 76.4
G1,2,x 93.7 95.2
Age < 60 yrs 39.9 38.6
ER+/PgR+ 81.1 81.3
ER+/PgR- 18.3 18.1
ER-/PgR+ 0.6 0.6
Patient demographics
Gx = lobular carcinoma