arr;DH (n = 1074)
Hazard Ratio vs AC→D
(95% CI)
p-value
Disease-free survival
No. patients with event
195
134
0.61 (0.49, 0.77)
p < 0.0001
Distant recurrence
No. patients with event
144
95
0.59 (0.46, 0.77)
p < 0.0001
Death (OS event)
No. patients with event
80
49
0.58 (0.40, 0.83)
p = 0.0024
AC→D = doxorubicin plus cyclophosphamide, followed by docetaxel; AC→DH = doxorubicin plus cyclophosphamide, followed by docetaxel plus trastuzumab; CI = confidence interval
Table 10 Overview of efficacy analyses BCIRG 006 AC→D versus DCarbH
Parameter
AC→D
(n = 1073)
DCarbH
(n = 1074)
Hazard Ratio vs AC→D
(95% CI)
Disease-free survival
No. patients with event
195
145
0.67 (0.54, 0.83)
p = 0.0003
Distant recurrence
No. patients with event
144
103
0.65 (0.50, 0.84)
p = 0.0008
Death (OS event)
No. patients with event
80
56
0.66 (0.47, 0.93)
p = 0.0182
AC→D = doxorubicin plus cyclophosphamide, followed by docetaxel; DCarbH = docetaxel, carboplatin and trastuzumab; CI = confidence interval
In the BCIRG 006 study for the primary endpoint, DFS, the hazard ratio translates into an absolute benefit, in terms of 3-year disease-free survival rate estimates of 5.8 percentage points (86.7% versus 80.9%) in favour of the AC→DH (trastuzumab) arm and 4.6 percentage points (85.5% versus 80.9%) in favour of the DCarbH (trastuzumab) arm compared to AC→D.
In study BCIRG 006, 213/1075 patients in the DCarbH (TCH) arm, 221/1074 patients in the AC→DH (AC→TH) arm, and 217/1073 in the AC→D (AC→T) arm had a Karnofsky performance status ≤ 90 (either 80 or 90). No disease-free survival (DFS) benefit was noticed in this subgroup of patients (hazard ratio = 1.16, 95% CI [0.73, 1.83] for DCarbH (TCH) versus AC→D (AC→T); hazard ratio 0.97, 95% CI [0.60, 1.55] for AC→DH (AC→TH) versus AC→D).
In addition a post-hoc exploratory analysis was performed on the data sets from the joint analysis (JA) NSABP B-31/NCCTG N9831* and BCIRG 006 clinical studies combining DFS events and symptomatic cardiac events and summarised in table 11:
Table 11 Post-hoc exploratory analysis results from the joint analysis NSABP B-31/NCCTG N9831* and BCIRG 006 clinical studies combining DFS events and symptomatic cardiac events
AC→PH
(vs.AC→P)
(NSABP B-31 and NCCTG N9831)*
AC→DH
(vs. AC→D)
(BCIRG 006)
DCarbH
(vs. AC→D)
(BCIRG 006)
Primary efficacy analysis
DFS Hazard ratios
(95% CI)
p-value
0.48
(0.39, 0.59)
p < 0.0001
0.61
(0.49, 0.77)
p < 0.0001
0.67
(0.54, 0.83)
p = 0.0003
Long term follow-up efficacy analysis**
DFS Hazard ratios
(95% CI)
p-value
0.61
(0.54, 0.69)
p<0.0001
0.72
(0.61, 0.85)
p<0.0001
0.77
(0.65, 0.90)
p=0.0011
Post-hoc exploratory analysis with DFS and symptomatic cardiac events
Long term follow-up**
Hazard ratios
(95% CI)
0.67
(0.60, 0.75)
0.77
(0.66, 0.90)
0.77
(0.66, 0.90)
A: doxorubicin; C: cyclophosphamide; P: paclitaxel; D: docetaxel; Carb: carboplatin; H: trastuzumab CI = confidence interval
* At the time of the definitive analysis of DFS. Median duration of follow-up was 1.8 years in the AC→P arm and 2.0 years in the AC→PH arm
** Median duration of long term follow-up for the Joint Analysis clinical studies was 8.3 years (range: 0.1 to 12.1) for the AC&ra |
