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 recurrences 1 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 1 Goss PE et al. NEJM 2003; 349:

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) RANDOMIZERANDOMIZE 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 involvement 0 nodes 1-3 nodes >3 nodes Tumor grade G1 G2 G3 Gx Estrogen receptor status Positive Negative Unknown Progesterone receptor status Positive 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 Total (n=856) *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= There was no significant difference between groups for overall survival

Recurrence-free survival for loco-regional, contralateral and distant metastatic disease Recurrence- free patients (%) Time (months) Anastrozole No treatment HR 0.64 p=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 disease 1 1 ATAC 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 1 Goss PE et al. NEJM 2003; 349:

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 1 Winer EP et al. J Clin Oncol 2005; 23:

Conclusion Anastrozole is an effective extended adjuvant therapy that significantly reduces the risk of recurrence following 5 years’ treatment with tamoxifen