The phase III international multicenter clinical trial showed for the first time that use of the targeted therapy lapatinib with capecitabine was more effective against cancer growth than capecitabine alone in women with advanced HER2/neu positive breast cancer that had started to grow despite prior therapy that included trastuzumab.

In the current study, researchers compared time to progression between 160 women who were randomized to lapatinib plus capecitabine and 161 women who were randomized to capecitabine alone. All women had advanced or metastatic breast cancer that persisted despite prior therapy with an anthracycline drug, a taxane, and trastuzumab.

Time to progression was almost twice as long in the combination therapy group as in the capecitabine group: 36.9 weeks versus 19.7 weeks. Fewer women in the lapatinib group developed brain metastases (4 versus 11 women).

Side effects were generally similar between the two groups, although women in the lapatinib group were somewhat more likely to experience mild to moderate diarrhea (58 versus 39 percent) and rash (30 versus 18 percent).

“Trastuzumab is a very effective drug that has substantially improved the available treatments for women with metastatic breast cancer that produces large amounts of the HER2/neu protein. However, because trastuzumab eventually stops controlling these cancers, there is a need for effective alternative treatments that block the function of HER2/neu in another way,” said Charles E. Geyer, Jr., MD, Director of Breast Medical Oncology at Allegheny General Hospital in Pittsburgh, and lead author of the study.

“These results indicate that lapatinib can be effective in helping control the growth of breast cancers that are not being controlled by trastuzumab.”

The HER2/neu receptor is over-expressed in approximately 20 to 25 percent of breast cancers. Trastuzumab blocks receptor activity by binding to the external part of the receptor. In contrast, lapatinib blocks enzyme activity by binding to the internal part of the receptor.

Laboratory studies have indicated it could be effective in controlling breast cancers that have become resistant to trastuzumab. Capecitabine has been approved for use in the USA to treat advanced breast cancer that has continued to grow despite prior therapy. Both lapatinib and capecitabine are taken orally.