l (months) (95%CI)
16.4
(12.3-ne)
24.8
(18.6-33.7)
17.9
(11.2-23.8)
31.2
(27.3-40.8)
22.74
(19.1-30.8)
TTP = time to progression; "ne" indicates that it could not be estimated or it was not yet reached.
1. Study H0649g: IHC3+ patient subset
2. Study H0648g: IHC3+ patient subset
3. Study M77001: Full analysis set (intent-to-treat), 24 months results
Combination treatment with trastuzumab and anastrozole
Trastuzumab has been studied in combination with anastrozole for first line treatment of MBC in HER2 overexpressing, hormone-receptor (i.e. oestrogen-receptor (ER) and/or progesterone-receptor (PR)) positive postmenopausal patients. Progression free survival was doubled in the trastuzumab plus anastrozole arm compared to anastrozole (4.8 months versus 2.4 months). For the other parameters the improvements seen for the combination were for overall response (16.5% versus 6.7%); clinical benefit rate (42.7% versus 27.9%); time to progression (4.8 months versus 2.4 months). For time to response and duration of response no difference could be recorded between the arms. The median overall survival was extended by 4.6 months for patients in the combination arm. The difference was not statistically significant, however more than half of the patients in the anastrozole alone arm crossed over to a trastuzumab containing regimen after progression of disease.
Three-weekly dosing in metastatic breast cancer
The efficacy results from the non-comparative monotherapy and combination therapy studies are summarised in table 5:
Table 5 Efficacy results from the non-comparative monotherapy and combination therapy studies
Parameter
Monotherapy
Combination therapy
Trastuzumab1
N = 105
Trastuzumab2
N = 72
Trastuzumab plus paclitaxel3
N = 32
Trastuzumab plus docetaxel4
N = 110
Response rate
(95%CI)
24%
(15-35)
27%
(14-43)
59%
(41-76)
73%
(63-81)
Median duration of response (months) (range)
10.1
(2.8-35.6)
7.9
(2.1-18.8)
10.5
(1.8-21)
13.4
(2.1-55.1)
Median TTP (months) (95%CI)
3.4
(2.8-4.1)
7.7
(4.2-8.3)
12.2
(6.2-ne)
13.6
(11-16)
Median Survival (months) (95%CI)
ne
ne
ne
47.3
(32-ne)
TTP = time to progression; "ne" indicates that it could not be estimated or it was not yet reached.
1. Study WO16229: loading dose 8 mg/kg, followed by 6 mg/kg 3-weekly schedule
2. Study MO16982: loading dose 6 mg/kg weekly x 3; followed by 6 mg/kg 3-weekly schedule
3. Study BO15935
4. Study MO16419
Sites of progression
The frequency of progression in the liver was significantly reduced in patients treated with the combination of trastuzumab and paclitaxel, compared to paclitaxel alone (21.8% versus 45.7%; p = 0.004). More patients treated with trastuzumab and paclitaxel progressed in the central nervous system than those treated with paclitaxel alone (12.6% versus 6.5%; p = 0.377).
Early breast cancer (adjuvant setting)
EBC is defined as non-metastatic primary invasive carcinoma of the breast.
In the adjuvant treatment setting, trastuzumab was investigated in 4 large multicentre, randomised, trials.
- Study BO16348 was designed to compare one and two years of three-weekly trastuzumab treatment versus observation in patients with HER2 positive EBC following surgery, established chemotherapy and radiotherapy (if applicable). In addition, comparison of two years of trastuzumab treatment versus one year |
