of trastuzumab treatment was performed. Patients assigned to receive trastuzumab were given an initial loading dose of 8 mg/kg, followed by 6 mg/kg every three weeks for either one or two years.
- The NSABP B-31 and NCCTG N9831 studies that comprise the joint analysis were designed to investigate the clinical utility of combining trastuzumab treatment with paclitaxel following AC chemotherapy, additionally the NCCTG N9831 study also investigated adding trastuzumab sequentially to AC→P chemotherapy in patients with HER2 positive EBC following surgery.
- The BCIRG 006 study was designed to investigate combining trastuzumab treatment with docetaxel either following AC chemotherapy or in combination with docetaxel and carboplatin in patients with HER2 positive EBC following surgery.
EBC in the HERA trial was limited to operable, primary, invasive adenocarcinoma of the breast, with axillary nodes positive or axillary nodes negative if tumours at least 1 cm in diameter.
In the joint analysis of the NSABP B-31 and NCCTG N9831 studies, EBC was limited to women with operable breast cancer at high risk, defined as HER2-positive and axillary lymph node positive or HER2 positive and lymph node negative with high risk features (tumour size > 1 cm and ER negative or tumour size > 2 cm, regardless of hormonal status).
In the BCIRG 006 study HER2 positive, EBC was defined as either lymph node positive or high risk node negative patients with no (pN0) lymph node involvement, and at least 1 of the following factors: tumour size greater than 2 cm, oestrogen receptor and progesterone receptor negative, histological and/or nuclear grade 2-3, or age < 35 years).
The efficacy results from the BO16348 trial following 12 months* and 8 years** median follow-up are summarised in table 6:
Table 6 Efficacy results from study BO16348
Median follow-up
12 months*
Median follow-up
8 years**
Parameter
Observation
N = 1,693
Trastuzumab
1 Year
N = 1,693
Observation
N = 1697***
Trastuzumab
1 Year
N = 1,702***
Disease-free survival
- No. patients with event
- No. patients without event
P-value versus Observation
Hazard Ratio versus Observation
219 (12.9%)
1,474 (87.1%)
127 (7.5%)
1,566 (92.5%)
570 (33.6%)
1,127 (66.4%)
471 (27.7%)
1,231 (72.3%)
< 0.0001
0.54
< 0.0001
0.76
Recurrence-free survival
- No. patients with event
- No. patients without event
P-value versus Observation
Hazard Ratio versus Observation
208 (12.3%)
1,485 (87.7%)
113 (6.7%)
1,580 (93.3%)
506 (29.8%)
1,191 (70.2%)
399 23.4%)
1,303 (76.6%)
< 0.0001
0.51
< 0.0001
0.73
Distant disease-free survival
- No. patients with event
- No. patients without event
P-value versus Observation
Hazard Ratio versus Observation
184 (10.9%)
1,508 (89.1%)
99 (5.8%)
1,594 (94.6%)
488 (28.8%)
1,209 (71.2%)
399 (23.4%)
1,303 (76.6%)
< 0.0001
0.50
< 0.0001
0.76
Overall survival (death)
- No. patients with event
- No. patients without event
P-value versus Observation
Hazard Ratio versus Observation
40 (2.4%)
1,653 (97.6%)
31 (1.8%)
1,662 (98.2%)
350 (20.6%)
1,347 (79.4%)
278 (16.3%)
1,424 (83.7%)
0.24
0.75
0.0005
0.76
*Co-primary endpoint of DFS of 1 year versus observation met the pre-defined statistical boundary
**Final analysis (including cross-over of 52% of patients from the observation arm to trastuzumab)
***There is a discrep |
