(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 the 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:

- intravenous 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 summarized 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→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