objectives of the combined analysis of abcsg trial 8 and the german arno 95 trial

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