Conditions: Breast Cancer
Keywords: recurrent breast cancer HER2-positive breast cancer stage IV breast cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 652
Healthy volunteers: no

Brief summary:
This was a multi-center, multinational, randomized, open-label, Phase III study comparing combination taxane-based chemotherapy plus lapatinib to combination taxane-based chemotherapy plus trastuzumab in women with documented evidence of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) (by local or central laboratory testing) who had received no prior chemotherapy or HER2 targeted therapy in the metastatic setting.

Detailed description:
Subjects were stratified by

* Prior (neo) adjuvant HER2/neu targeted therapy (yes, no)
* Prior (neo) adjuvant taxane chemotherapy (yes, no)
* Planned taxane treatment (once weekly paclitaxel versus docetaxel once every 3 weeks)
* Liver metastasis (yes, no)

Subjects were randomized 1:1 to the following treatments to a planned sample size of approximately 600 subjects (to achieve 536 centrally confirmed HER2 positive subjects):

* Taxane based chemotherapy plus lapatinib for 24 weeks followed by single agent lapatinib
* Taxane based chemotherapy plus trastuzumab for 24 weeks followed by single agent trastuzumab

The choice of taxane (once weekly paclitaxel versus docetaxel once every 3 weeks) was at the discretion of the treating physician and was specified at the time of subject randomization.

A protocol-specified interim analysis was conducted on 27-Apr-2012, following which the participants in the Lapatinib plus taxane based chemotherapy arm could cross over to Taxane based chemotherapy plus Trastuzumab.

Arms:
arm 1: Plus taxane based chemotherapy arm 2: Plus taxane based chemotherapy.

Interventions: intervention 1: trastuzumab intervention 2: docetaxel intervention 3: lapatinib ditosylate intervention 4: paclitaxel
Intervention descriptions: intervention 1: IV q weekly (loading dose 4mg/kg; subsequent doses 2mg/kg) or IV q 3 weekly (loading dose 8mg/kg, subsequent doses 6mg/kg). intervention 2: 75mg/m2 IV q 3 weekly, day 1 of a 3 week cycle for 8 cycles plus G-CSF (when given together with lapatinib). intervention 3: 1250 mg once daily (while given with taxane). 1500mg once daily (when given alone after taxane completion). intervention 4: 80mg/m2 IV q weekly days 1, 8 and 15 of a 4-week cycle for 6 cycles.

Protocol document: