mab to paclitaxel chemotherapy resulted in a 52% decrease in the risk of disease recurrence. The hazard ratio translates into an absolute benefit, in terms of 3-year disease-free survival rate estimates of 11.8 percentage points (87.2% versus 75.4%) in favour of the AC→PH (trastuzumab) arm.
At the time of a safety update after a median of 3.5-3.8 years follow-up, an analysis of DFS reconfirms the magnitude of the benefit shown in the definitive analysis of DFS. Despite the cross-over to trastuzumab in the control arm, the addition of trastuzumab to paclitaxel chemotherapy resulted in a 52% decrease in the risk of disease recurrence. The addition of trastuzumab to paclitaxel chemotherapy also resulted in a 37% decrease in the risk of death.
The pre-planned final analysis of OS from the joint analysis of studies NSABP B-31 and NCCTG N9831 was performed when 707 deaths had occurred (median follow-up 8.3 years in the AC→PH group). Treatment with AC→PH resulted in a statistically significant improvement in OS compared with AC→P (stratified HR = 0.64; 95% CI [0.55, 0.74]; log-rank p-value < 0.0001). At 8 years, the survival rate was estimated to be 86.9% in the AC→PH arm and 79.4% in the AC→P arm, an absolute benefit of 7.4% (95% CI 4.9%, 10.0%).
The final OS results from the joint analysis of studies NSABP B-31 and NCCTG N9831 are summarised in table 8:
Table 8 Final overall survival analysis from the joint analysis of trials NSABP B-31 and NCCTG N9831
Parameter
AC→P
(N = 2032)
AC→PH
(N = 2031)
p-value versus AC→P
Hazard Ratio versus AC→P
(95% CI)
Death (OS event):
No. patients with event (%)
418 (20.6%)
289 (14.2%)
< 0.0001
0.64
(0.55, 0.74)
A: doxorubicin; C: cyclophosphamide; P: paclitaxel; H: trastuzumab
DFS analysis was also performed at the final analysis of OS from the joint analysis of studies NSABP B-31 and NCCTG N9831. The updated DFS analysis results (stratified HR = 0.61; 95% CI [0.54, 0.69]) showed a similar DFS benefit compared to the definitive primary DFS analysis, despite 24.8% patients in the AC→P arm who crossed over to receive trastuzumab. At 8 years, the disease-free survival rate was estimated to be 77.2% (95% CI: 75.4, 79.1) in the AC→PH arm, an absolute benefit of 11.8% compared with the AC→P arm.
In the BCIRG 006 study trastuzumab was administered either in combination with docetaxel, following AC chemotherapy (AC→DH) or in combination with docetaxel and carboplatin (DCarbH).
Docetaxel was administered as follows:
- intavenous docetaxel – 100 mg/m2 as an intravenous infusion over 1 hour, given every 3 weeks for 4 cycles (day 2 of first docetaxel cycle, then day 1 of each subsequent cycle)
or
- intravenous docetaxel – 75 mg/m2 as an intravenous infusion over 1 hour, given every 3 weeks for 6 cycles (day 2 of cycle 1, then day 1 of each subsequent cycle)
which was followed by:
- carboplatin – at target AUC = 6 mg/mL/min administered by intravenous infusion over 30-60 minutes repeated every 3 weeks for a total of six cycles
Trastuzumab was administered weekly with chemotherapy and 3-weekly thereafter for a total of 52 weeks.
The efficacy results from the BCIRG 006 are summarised in Tables 9 and 10. The median duration of follow-up was 2.9 years in the AC→D arm and 3.0 years in each of the AC→DH and DCarbH arms.
Table 9 Overview of efficacy analyses BCIRG 006 AC→D versus AC→DH
Parameter
AC→D
(n = 1073)
AC&r |
