Objectives of the combined analysis of ABCSG Trial 8 and the German ARNO 95 trial
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Transcript of Objectives of the combined analysis of ABCSG Trial 8 and the German ARNO 95 trial
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Postmenopausal women currently on adjuvant tamoxifen
should be switched to anastrozole
after 2 years of treatment
Conclusion
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Back up slides
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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