AROMASIN^® improves disease-free survival vs continuing on tamoxifen

• The Intergroup Exemestane Study (IES) is a large, landmark switch trial with patients representative of the general breast cancer population
• Objective:
  • To determine if, after 2 to 3 years of tamoxifen, switching to AROMASIN 25 mg daily was more effective than continuing tamoxifen therapy for the remainder of the 5-year treatment period^[1] (Figure 1-1)
• Study design:
• Multinational, randomized, double-blind, phase 3 trial^[1]
• Study was conducted in 37 countries, and 366 centers^[1,2]
• 4724 postmenopausal women in the intent-to-treat analysis with estrogen-receptor (ER) positive or ER unknown breast cancer were randomized to AROMASIN 25 mg once daily (n=2352) or continued on tamoxifen once daily^[3] (n=2372) (Table 1-1) (Figure 1-1)
• Patients were randomized after remaining disease free on adjuvant tamoxifen for 2 to 3 years^[1]



Figure 1-1. IES design. *Patients in Denmark received 30 mg/d, which is the standard care in that country.^[1,2]


• The 2 treatment groups were well balanced at baseline (Table 1-1). 85% of patients were ER+^[3]
• Postoperative radiotherapy and adjuvant chemotherapy were permitted^[1]



Intent-to-treat (ITT) population (N=4724)

Parameter AROMASIN Tamoxifen n 2352 2372 Median age (range) 63 (38-96) 63 (31-90) Race (%) Caucasian 98.4 98.4 Other (including Hispanic, Asian, Black) 1.6 1.6 Nodal status (%) Negative 51.7 51.8 Positive 44.7 44.0 Receptor status (%) ER+ and PgR+ 56.6 55.6 ER+ and PgR-/unknown 28.8 29.2 ER- and PgR+ 0.3 0.3 Histologic type (%) Infiltrating ductal 75.6 77.2 Infiltrating lobular 14.5 13.5 Other 9.8 9.0

Table 1-1. Demographics and Baseline Patient Characteristics in IES Trial ITT Population (N = 4724)^[3]
ER = estrogen receptor; PgR = progesterone receptor.

• Median follow-up: 34.5 months and 52.4 months^[2]
• Primary end point: Disease-free survival (DFS), defined as the time from randomization to time of local or distant recurrence of breast cancer, contralateral breast cancer, or death from any cause. The study is powered to show a 3.6% difference in DFS after 3 years^[1]
• Secondary end point: Overall survival (OS), time to contralateral breast cancer, distant recurrence-free survival, and long-term tolerability^[1]

• Key efficacy data from IES were released after the second interim analysis, at which time the O'Brien-Fleming stopping boundary (P = 0.004) had been exceeded. At the time of this release, over 90% of patients in both treatment groups had completed treatment^[1]

IES efficacy data from 34.5-month median follow-up

• Patients switching to AROMASIN experienced statistically significant benefits for disease-free survival (hazard ratio [HR] = 0.69; P = 0.00003; Table 1-2; Figure 1-2)^[3] and time to contralateral breast cancer (HR = 0.32; P = 0.0034; Table 1-2)^[3]

• 4% absolute difference in DFS at 3 years after randomization^[3]
• 35% relative risk reduction for DFS for HR+ patients (HR = 0.65; 95% CI, 0.53-0.79; P = 0.00001)^[3] (Table 1-2)
• Overall survival was not statistically different between the 2 groups^[3] (Table 1-2)
• 14% relative risk reduction for ITT population (HR=0.86; 95% CI, 0.67-1.10,
  P=0.23)
• 12% relative risk reduction for HR+ population (HR=0.88; 95% CI, 0.67-1.17,
  P=0.37)
• Consistent results in patients with node positive or node negative disease, and with or without prior chemotherapy (Figure 1-3)

IES Landmark Study long term follow up

"This updated analysis of IES lends support to the rationale for switching adjuvant therapy to exemestane after 2-3 years of tamoxifen in postmenopausal women who remain free of recurrence after treatment for early breast cancer"^[4]

IES efficacy and safety data from 52.4-month median follow-up

• Patients switching to AROMASIN experienced statistically significant benefits for disease-free survival (HR = 0.76 and P < 0.001)^[2] (Table 1-3)

• The ITT population: ER+ and ER- and ER unknown patients

• ER+/unknown population: some patients originally categorized as ER unknown
  (n = 551; 11.7%) were ultimately determined to be ER- (n = 123; 2.6%) and therefore excluded from this analysis

• Switching to AROMASIN resulted in a 24% relative risk reduction in DFS and a 3.4% absolute difference at 3 years after randomization (ITT population)^[2]
• 25% relative risk reduction in DFS in ER+/unknown patients after switching to AROMASIN^[2]

IES safety data from 32 month follow-up

• AROMASIN was generally well tolerated and adverse events were usually mild to moderate^[3] (Table 1-4)
• Discontinuation due to adverse events occurred in 6.3% and 5.1% of patients receiving AROMASIN and tamoxifen, respectively^[3]
• Deaths due to any cause were reported for 1.3% of patients treated with AROMASIN and 1.4% of the tamoxifen-treated patients^[3]
• There were 6 deaths due to stroke in the AROMASIN arm compared with 2 in the tamoxifen arm^[3]
• There were 5 deaths due to cardiac failure in the AROMASIN arm compared with 2 in the tamoxifen arm^[3]

Most common adverse events (AEs) after long-term follow-up

• The most common AEs observed at the 52.4-month median follow-up were similar to those observed at the 34.5-month median follow-up^[2,3]
• At the 52.4-month median follow-up, patients taking AROMASIN experienced a significant increase in the overall fracture rate vs tamoxifen: 7% vs 4.9%
  (P = 0.002)^[2]
• Reductions in bone mineral density over time are seen with use of AROMASIN^[3]  Learn more...