One-third of women with HER2-positive metastatic breast cancer currently develop brain metastases.
Once the disease advances to this stage, overall disease prognosis is poor with the average one-year survival from diagnosis estimated at about 20 percent.

Results from an ongoing, multicenter Phase II study suggest that Lapatinib ( Tykerb ) has clinical activity in pretreated patients with brain metastases from HER2-positive breast cancer.

Patients ( n=241 ) enrolled in this study had radiographically documented progressive brain lesions following prior therapy with Trastuzumab (Herceptin ) and cranial radiotherapy.

Results from an independent radiology review show that 19 patients ( 7% ) treated with Lapatinib monotherapy experienced a partial response, defined by greater than or equal to 50% volumetric reduction in brain lesions with no progression of tumor outside the brain, no increase in steroid requirements or worsening of neurological symptoms.
Forty-six patients ( 19% ) experienced greater than or equal to 20% volumetric reduction in brain lesions.

An additional 102 patients ( 42% ) achieved stable disease for at least eight weeks based on a protocol defined composite response criteria.
Twenty-two percent of all patients had no disease progression within the first six months on Lapatinib monotherapy.

An exploratory analysis in a previous, Phase III study found that numerically fewer patients on Lapatinib plus Capecitabine ( Xeloda ) developed brain metastases as compared to Capecitabine alone.
As a result, this Phase II study was amended to allow patients whose disease progressed in the brain and/or non-CNS on monotherapy Lapatinib to then receive the combination of Lapatinib and Capecitabine.
In patients ( n=40 ) treated with Lapatinib in combination with Capecitabine, 8 ( 20% ) experienced greater than or equal to 50% volume reduction in brain metastases, and 16 ( 40% ) experienced greater than or equal to 20% volume reduction.

The most common adverse events included diarrhoea ( 13% Grades 3 and 4 ), skin rash ( 3% Grades 3 and 4 ), nausea ( 3% Grade 3 ), vomiting ( 4% Grade 3 ), fatigue ( 3% Grade 3 ) and anorexia ( 1% Grade 3 ).

Source: American Society of Clinical Oncology ( ASCO ) – Annual Meeting, 2007

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