and 2, theduration of DFS following a median follow-up of 2.0 years in the AC→TH arm is presented in Figure 4,and the duration of OS after a median follow-up of 8.3 years in the AC→TH arm is presented in Figure 5.
The duration of DFS for Study 4 is presented in Figure 6. Across all four studies, at the time of definitiveDFS analysis, there were insufficient numbers of patients within each of the following subgroups todetermine if the treatment effect was different from that of the overall patient population: patients with low
tumor grade, patients within specific ethnic/racial subgroups (Black, Hispanic, Asian/Pacific Islanderpatients), and patients > 65 years of age. For Studies 1 and 2, the OS hazard ratio was 0.64 (95% CI: 0.55,0.74). At 8.3 years of median follow up [AC→TH], the survival rate was estimated to be 86.9% in theAC→TH arm and 79.4% in the AC→T arm. The final OS analysis results from Studies 1 and 2 indicate thatOS benefit by age, hormone receptor status, number of positive lymph nodes, tumor size and grade, andsurgery/radiation therapy was consistent with the treatment effect in the overall population. In patients ≤ 50years of age (n = 2197), the OS hazard ratio was 0.65 (95% CI: 0.52, 0.81) and in patients > 50 years of age(n = 1866), the OS hazard ratio was 0.63 (95% CI: 0.51, 0.78). In the subgroup of patients with hormonereceptor-positive disease (ER-positive and/or PR-positive) (n = 2223), the hazard ratio for OS was 0.63(95% CI: 0.51, 0.78). In the subgroup of patients with hormone receptor-negative disease (ER-negative andPR-negative) (n = 1830), the hazard ratio for OS was 0.64 (95% CI: 0.52, 0.80). In the subgroup of patients
with tumor size ≤ 2 cm (n = 1604), the hazard ratio for OS was 0.52 (95% CI: 0.39, 0.71). In the subgroupof patients with tumor size > 2 cm (n = 2448), the hazard ratio for OS was 0.67 (95% CI: 0.56, 0.80).
Table 9
Efficacy Results from Adjuvant Treatment of Breast Cancer (Studies 1 + 2, Study 3, and Study 4)
DFS Hazard
ratio
DFS (95% CI) Deaths OS Hazard ratio
events p-value (OS events) p-value
Studies 1 + 2a
AC→TH
(n = 1872)b
(n 2031)c
133
b
0.48
b,d
(0.39,
0.59) p ˂
0.0001e
289c 0.64c,d
(0.55, 0.74)
p ˂ 0.0001e
AC→T 261b 418c
(n = 1880)
b
(n 2032)c
Study 3f
Chemo→
Trastuzumab
(n = 1693)
127 0.54
(0.44, 0.67) p
˂ 0.0001g
31 0.75
p = NSh
Chemo→ 219 40
Observation
(n = 1693)
Study 4i
TCH 134 0.67 56
(n = 1075) (0.54 – 0.84) p
= 0.0006e,j
AC→TH 121 0.60 49
(n = 1074) (0.48 – 0.76) p
< 0.0001e,i
AC→T
(n = 1073)
180 80
CI = confidence interval.
a Studies 1 and 2 regimens: doxorubicin and cyclophosphamide followed by paclitaxel(AC→T) or paclitaxel plus trastuzumab (AC→TH).
b Efficacy eva luable population, for the primary DFS analysis, following a medianfollow-up of 2.0 years in the AC→TH arm. c Efficacy eva luable population, for the final OS analysis, following 707 deaths (8.3years of median follow-up in the AC→TH arm).
d Hazard ratio estimated by Cox regression stratified by clinical trial, intended paclitaxelschedule, number of positive nodes, and hormone receptor status. e stratified log-rank test.
f At definitive DFS analysis with median duration of follow-up of 12.6 months in theone-year trastuzumab treatment arm. g log-rank test.
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