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)

Early breast cancer 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 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.

Early breast cancer 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, estrogen 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 summarized in Table 6:

Table 6 Efficacy results from Study BO16348

Median follow-up

12 months*

Median follow-up

8 years**

Parameter

Observation

N=1693