vour of the Herceptin arm.
In the NCCTG N9831 and NSABP B-31 studies Herceptin was administered in combination with paclitaxel, following AC chemotherapy.
Doxorubicin and cyclophosphamide were administered concurrently as follows:
- intravenous push doxorubicin, at 60 mg/ m2, given every 3 weeks for 4 cycles.
- intravenous cyclophosphamide, at 600 mg/ m2 over 30 minutes, given every 3 weeks for 4 cycles.
Paclitaxel, in combination with Herceptin, was administered as follows:
- intravenous paclitaxel - 80 mg/m2 as a continuous i.v. infusion, given every week for 12 weeks.
or
- intravenous paclitaxel - 175 mg/m2 as a continuous i.v. infusion, given every 3 weeks for 4 cycles (day 1 of each cycle).
The efficacy results from the joint analysis of the NCCTG 9831 and NSABP B-31 trials are summarized in the table below. The median duration of follow up was 1.8 years for the patients in the ACP arm and 2.0 years for patients in the ACPH arm.
|
Parameter
|
AC P
(n=1697)
|
ACPH
(n=1672)
|
Hazard Ratio vs ACP
(95% CI)
p-value
|
|
Disease-free survival
No. patients with event (%)
|
261 (15.4)
|
133 (7.9)
|
0.48 (0.39, 0.59)
p<0.0001
|
|
Distant Recurrence
No. patients with event
|
174
|
90
|
0.47 (0.37, 0.60)
p<0.0001
|
|
Death (OS event):
No. patients with event
|
92
|
62
|
0.67 (0.48, 0.92)
p=0.014
|
A: doxorubicin; C: cyclophosphamide; P: paclitaxel; H: trastuzumab
For the primary endpoint, DFS, the addition of Herceptin 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 % vs 75.4 %) in favour of the ACPH (Herceptin) 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 Herceptin in the control arm, the addition of Herceptin to paclitaxel chemotherapy resulted in a 52% decrease in the risk of disease recurrence. The addition of Herceptin to paclitaxel chemotherapy also resulted in a 37% decrease in the risk of death.
In the BCIRG 006 study Herceptin was administered either in combination with docetaxel, following AC chemotherapy (ACDH) or in combination with docetaxel and carboplatin (DCarbH).
Docetaxel was administered as follows:
- intravenous docetaxel - 100 mg/m2 as an i.v. 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 i.v. infusion over 1 hour, given every 3 weeks for 6 cycles (day 2 of cycle 1, then day 1 of each subsequent cycle)
|
