e 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 BCIRG006 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 BCIRG006 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
0.48
0.61
0.67
(95% CI)
(0.39, 0.59)
(0.49, 0.77)
(0.54, 0.83)
p-value
p<0.0001
p<0.0001
p=0.0003
Long term follow-up efficacy analysis**
DFS hazard ratios
0.61
0.72
0.77
(95% CI)
(0.54, 0.69)
(0.61, 0.85)
(0.65, 0.90)
p-value
p<0.0001
p<0.0001
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→PH arm and 7.9 years (range: 0.0 to 12.2) for the AC→P arm; Median duration of long term follow-up for the BCIRG 006 study was 10.3 years in both the AC→D arm (range: 0.0 to 12.6) arm and the DCarbH arm (range: 0.0 to 13.1), and was 10.4 years (range: 0.0 to 12.7) in the AC→DH arm
Early breast cancer (neoadjuvant-adjuvant setting)
So far, no results are available which compare the efficacy of trastuzumab administered with chemotherapy in the adjuvant setting with that obtained in the neo-adjuvant/adjuvant setting.
In the neoadjuvant-adjuvant treatment setting, study MO16432, a multicentre randomised trial, was designed to investigate the clinical efficacy of concurrent administration of trastuzumab with neoadjuvant chemotherapy including both an anthracycline and a taxane, followed by adjuvant trastuzumab, up to a total treatment duration of 1 year. The study recruited patients with newly diagnosed locally advanced (Stage III) or inflammatory EBC. Patients with HER2+ tumours were randomised to receive either neoadjuvant chemotherapy concurrently
