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.

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.

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

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.

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% 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

Event-free survival Event-free survival (%) ANA TAM ANA vs TAM 100 ANA 95 90 TAM 85 80 ANA vs TAM p=0.0009 HR 0.60 [95% CI 0.44-0.81] 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 0.59 ......... 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

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 0.42-0.87] 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

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)

Overall survival 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 We currently have no data indicating a significant difference in terms of OS – there are not enough events.

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

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.

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.

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

Back up slides