1. 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
I’ll now present to you prospective data generated by the Austrian and German Groups.
The analysis covers postmenopausal breast cancer patients - all receptor-positive - switching from TAM to ANA, as compared to patients receiving TAM alone.

2. Objectives of the combined analysis of ABCSG Trial 8 and the German 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
I’ll now present to you prospective data generated by the Austrian and German Groups.
The analysis covers postmenopausal breast cancer patients - all receptor-positive - switching from TAM to ANA, as compared to patients receiving TAM alone.

3. Trial endpoints Primary endpoint Secondary endpoints include
Event-free survival (EFS)
Secondary endpoints include
Distant recurrence-free survival (DRFS)
Tolerability
EFS was the primary endpoint for our combined analysis.
An event was defined either as locoregional relapse, as distant metastasis, or as contralateral breast cancer.
Distant recurrence-free survival and tolerability were selected as secondary endpoints.
Events = locoregional recurrences, distant metastases, contralateral breast cancer

4. ABCSG 8 – ARNO 95: Combined analysis trial structure
Total patients
n=3,224
ABCSG 8
n=2,262 +
ARNO 95
n=962
TAM 3 years
n=1,606
Primary
surgery
+/- RTx
+ TAM
2 years
ANA 3 years
n=1,618
The results were generated from a combined analysis of 3,224 patients who received
- either 3 years of TAM
- or 3 years of ANA
after primary surgery and exposure to 2 years of TAM.

5. Event-free survival: 28 months median follow-up
Number Events 3yrs EFS
n=3, n=177
TAM 1, %
ANA 1, %
The following data is most interesting:
Of 177 events, 110 were observed in the TAM arm and 67 in the ANA arm at a median of 28 months follow-up.
3 years EFS was 93% in the group treated with TAM and 96% in patients receiving ANA.
Events = locoregional recurrences, distant metastases, contralateral breast cancer

6. Event-free survival Event-free survival (%) ANA TAM ANA vs TAM
100
ANA 95 90
TAM 85 80
ANA vs TAM
p= HR 0.60 [95% CI ] 75
This Kaplan Meier plot of EFS demonstrates the highly significant benefit for our patients switching to ANA after 2 years of TAM over those remaining on TAM.
The HR was A truely impressive outcome ! 1 2 3 4 5
EFS time in years*
At risk:
TAM
1606
1217
858
593
343
176
ANA
1618
1243
874
623
375
178
*Zero point = 2 years after surgery

7. Distant recurrence-free survival
100
Distant recurrence-free survival (%)
ANA 96 92
TAM 88
ANA
ANA vs vs
TAM
TAM 84 p p
=0.0067
=0.0067
HR 0.61 [95% CI ]
The different rates of distant metastases are graphically shown in a Kaplan Meier plot with a HR of 0.6. 1 2 3 4 5
At risk:
DRFS time in years
TAM
ANA
1606
1224
1247
869
879
600
631
351
181
1618
382
181
*Zero point = 2 years after surgery

8. Subgroup analysis of EFS
3,224
2,389
833
3,044
167
1,265
1,959
2,519
564
All patients
Nodal status -ve
+ve
Grading G1, G2, Gx G3
Age <60 years
60 years
Receptor (ER / PR) +ve / +ve
+ve / -ve
The Forest plot, based on a subgroup analysis of EFS, shows that sequential treatment is beneficial irrespective of nodal status, age, and receptor status.
There are too few patients with undifferentiated tumors to gain clear information in this respect.
0.25
0.50
0.80
1.00
1.25
1.50
2.00
3.00
ANA better
TAM better
Hazard ratio (ANA vs TAM)

9. Overall survival Number Deaths 3 yrs. OS (%) TAM 1,606 59 96.4
ANA 1,
ANA vs TAM p=0.16 HR 0.76 95% CI 
We currently have no data indicating a significant difference in terms of OS – there are not enough events.

10. 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

11. Summary
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
In summary, our efficacy analyses have clearly demonstrated that switching treatment to ANA, subsequent to 2 years of TAM, is superior to staying on TAM.
Remarkably, the benefits of such sequential treatment are irrespective of our patients‘ nodal status and age.
It seems that ANA is more effective in better differentiated tumors.

12. Main question for the future
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
Now, what we do know currently is that ANA is superior to TAM,
when applied as 5-year primary adjuvant treatment, as ATAC has shown,
and second,when patients are switched from TAM to ANA, as I have just demonstrated.
What we still need to explore is whether one of these approaches is more appropriate than the other.

13. after 2 years of treatment
Conclusion
Postmenopausal women currently on adjuvant tamoxifen should be switched to anastrozole
after 2 years of treatment

14. Back up slides