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 6

Tamoxifen +/- aminoglutethemide

5 years (n=856)

R

A

N

D

O

M

I

Z

E

Anastrozole 3 years(n=387)

No treatment 3 years(n=469)

ABCSG Trial 6a

ABCSG Trial 6a schema

Disease characteristics of re-randomized patients

Nodal involvement0 nodes

1-3 nodes

>3 nodes

Tumor gradeG1

G2

G3

Gx

Estrogen receptor statusPositive

Negative

Unknown

Progesterone receptor statusPositive

Negative

Unknown

Anastrozole group (n, %)

No treatment group (n, %)

Characteristic

255 (65.9)

104 (26.8)

28 (7.3)

60 (15.5)

220 (56.9)

79 (20.4)

28 (7.2)

362 (93.5)

10 (2.6)

15 (3.9)

319 (82.4)

52 (13.5)

16 (4.1)

323 (68.9)

112 (23.9)

34 (7.3)

86 (18.3)

256 (54.6)

92 (19.6)

35 (7.5)

447 (95.3)

9 (2.0)

13 (2.8)

367 (78.3)

88 (18.8)

14 (3.0)

Incidence of disease recurrence in ABCSG Trial 6a

Loco-regional

Distant metastatic

Contralateral

Total*

Other secondary tumors

Anastrozole group (n=387)

No treatment group (n=469)

Recurrence event

10

16

6

30

18

Total(n=856)

15

35

10

56

23

25

51

16

86

41

*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-freepatients(%) 75

50

25

0

100

0 2412 36 48 60 72 84Time (months)

AnastrozoleNo treatment

HR 0.64p=0.0477

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 follow-up 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