l rate was estimated to be 86.9% in the AC→TH arm and 79.4% in the AC→T arm. Thefinal OS analysis results from Studies 1 and 2 indicate that OS benefit by age, hormone receptor status, numberof positive lymph nodes, tumor size and grade, and surgery/radiation therapy was consistent with the treatment
effect in the overall population. In patients ≤ 50 years 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.63 (95% CI: 0.51, 0.78). In the subgroup of patients with hormone receptor-positive disease (ER-positiveand/or PR-positive) (n = 2223), the hazard ratio for OS was 0.63 (95% CI: 0.51, 0.78). In the subgroup ofpatients with hormone receptor-negative disease (ER-negative and PR-negative) (n = 1830), the hazard ratio forOS was 0.64 (95% CI: 0.52, 0.80). In the subgroup of patients with tumor size ≤ 2 cm (n = 1604), the hazardratio for OS was 0.52 (95% CI: 0.39, 0.71). In the subgroup of patients with tumor size > 2 cm (n = 2448), thehazard 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 events DFS Hazard ratio Deaths OS Hazard ratio(95% CI) (OS events) p-value
p-value
Studies 1 + 2a
AC→TH 133b 0.48b,d 289c 0.64c,d
(n = 1872)b (0.39, 0.59) (0.55, 0.74)
(n = 2031)c p< 0.0001e p< 0.0001e
AC→T 261b 418c
(n = 1880)b
(n = 2032)c
Study 3f
Chemo→ 127 0.54 31 0.75
Trastuzumab (0.44, 0.67) p = NSh
(n = 1693) p< 0.0001g
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 paclitaxelplus trastuzumab (AC→TH).
b Efficacy eva luable population, for the primary DFS analysis, following a median follow-up of 2.0 years in theAC→TH arm. c Efficacy eva luable population, for the final OS analysis, following 707 deaths (8.3 years of median follow-upin the AC→TH arm).
d Hazard ratio estimated by Cox regression stratified by clinical trial, intended paclitaxel schedule, number ofpositive 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 the one-year trastuzumabtreatment arm.
g log-rank test.
h NS = non-significant.
i Study 4 regimens: doxorubicin and cyclophosphamide followed by docetaxel (AC→T) or docetaxel plustrastuzumab (AC→TH); docetaxel and carboplatin plus trastuzumab (TCH).
j A two-sided alpha level of 0.025 for each comparison.
Figure 4
Duration of Disease-Free Survival in Patients with Adjuvant Treatment of Breast Cancer (Studies 1 and 2)
Figure 5
Duration of Overall Survival in Patients with Adjuvant Treatment of Breast Cancer (Studies 1 and 2)
Figure 6
Duration of Disease-Free Survival in Patients with Adjuvant Treatment of Breast Cancer (Study 4)Exploratory analyses of DFS as a function of HER2 overexpression or gene amplification were conducted forpatients in Studies 2 and 3, where central laboratory testing data were available. The results are shown in
Table 10. The number of events in Study 2 was small with the exception of the IHC 3+/FISH+ subg |
