sp; Distant Recurrence 140 167
Distant Recurrence (first or subsequent events)
Contralateral Breast Cancer 142
37 169
53 0.88 (0.70,1.10) 0.246
Deaths Without Recurrence or Contralateral Breast Cancer 135 116
1 Adjusted by receptor status, nodal status and prior chemotherapy
2 Stratified logrank test, stratified by receptor status, nodal status and prior chemotherapy
3 DFS events defined as earliest of loco-regional recurrence, distant metastasis, contralateral breast cancer or death from any cause, and ignoring switches to Femara in 60% of the placebo arm.
4 Protocol definition does not include deaths from any cause
Updated analyses were conducted at a median follow-up of 62 months. In the Femara arm, 71% of the patients were treated for a least 3 years and 58% of patients completed at least 4.5 years of extended adjuvant treatment. After the unblinding of the study at a median follow-up of 28 months, approximately 60% of the selected patients in the placebo arm opted to switch to Femara.
In this updated analysis shown in Table 9, Femara significantly reduced the risk of breast cancer recurrence or contralateral breast cancer compared with placebo (HR 0.75; 95% CI 0.63, 0.89; P=0.001). However, in the updated DFS analysis (interval between randomization and earliest event of loco-regional recurrence, distant metastasis, contralateral breast cancer, or death from any cause) the treatment difference was heavily diluted by 60% of the patients in the placebo arm switching to Femara and accounting for 64% of the total placebo patient-years of follow-up. Ignoring these switches, the risk of DFS event was reduced by a non-significant 11% (HR 0.89; 95% CI 0.77, 1.03). There was no significant difference in distant disease-free survival or overall survival.
14.4 First-Line Treatment of Advanced Breast CancerA randomized, double-blind, multinational trial compared Femara 2.5 mg with tamoxifen 20 mg in 916 postmenopausal patients with locally advanced (Stage IIIB or loco-regional recurrence not amenable to treatment with surgery or radiation) or metastatic breast cancer. Time to progression (TTP) was the primary endpoint of the trial. Selected baseline characteristics for this study are shown in Table 10.
Table 10: Selected Study Population Demographics Baseline Status Femara tamoxifen
N=458 N=458
Stage of Disease
IIIB 6% 7%
IV 93% 92%
Receptor Status
ER and PgR Positive 38% 41%
ER or PgR Positive 26% 26%
Both Unknown 34% 33%
ER- or PgR-/Other Unknown <1% 0
Previous Antiestrogen Therapy
Adjuvant 19% 18%
None 81% 82%
Dominant Site of Disease
Soft Tissue 25% 25%
Bone 32% 29%
Viscera 43% 46%
Femara was superior to tamoxifen in TTP and rate of objective tumor respo |
