Women with HER-2 positive breast cancer whose disease progressed following treatment with trastuzumab (Herceptin) benefited from taking the experimental drug lapatinib along with the standard treatment, capecitabine, researchers said last week at the American Society of Clinical Oncology (ASCO) annual meeting in Atlanta.

The combination therapy delayed the growth or the spread of the cancer by about 4 months compared with capecitabine alone (8.5 months vs. 4.5 months).

"We believe that this is an effective regimen for women with HER-2 positive breast cancer and should be the new standard of care (for treating these women after trastuzumab fails)," said Dr. Charles E. Geyer, Jr., of the Allegheny General Hospital in Pittsburgh, who led the trial and presented the results at ASCO.

Lapatinib, or Tykerb, inhibits two proteins involved in cancer, the epidermal growth factor receptor (EGFR) and HER-2, which is also targeted by trastuzumab. HER-2 sits on the surface of cells, and trastuzumab binds the part outside the cell, while lapatinib binds the part inside the cell.

Trastuzumab has helped many women with HER-2 positive tumors, but the drug eventually stops working in some women. Tumors that produce excess amounts of the HER-2 protein - about 20 to 25 percent of breast cancers - are often aggressive and likely to recur.

"This study is good news," said Dr. Jo Anne Zujewski of NCI's Cancer Therapy Evaluation Program. "Lapatinib is an oral drug that is effective in women who have progressed following trastuzumab therapy."

The new regimen was generally well tolerated, Dr. Geyer reported. The addition of lapatinib to capecitabine did not appear to increase side effects significantly, although some women experienced mild diarrhea and rashes.

Dr. Geyer said that the cardiac health of women in the study was monitored very carefully and no major events were reported.

Fewer women in the combination group than in the capecitabine group experienced a recurrence of the cancer in the brain (4 women vs. 11 women). Unlike trastuzumab, lapatinib is a small molecule that may cross the blood-brain barrier and may be active in the brain.

The phase III study randomly assigned 160 women to receive lapatinib plus capecitabine and 161 women to receive capecitabine alone. All of the women had advanced or metastatic breast cancer that had recurred or progressed following prior therapy with an anthracycline drug, a taxane, and trastuzumab.

The inhibition of lapatinib's second target, EGFR, may not benefit women with breast cancer but could make the drug useful against other cancers, said Dr. Julie Gralow of the University of Washington, who commented on the study at ASCO.

Lapatinib is currently in clinical trials for advanced kidney cancer. The trial's leader, Dr. Alain Ravaud of the University Hospital of Bordeaux, France, said at ASCO that the drug appeared to benefit patients whose tumors produce high levels of the EGFR protein.

GlaxoSmithKline intends to seek FDA approval for lapatinib as a treatment for breast cancer this year. The company said it would soon make the drug available through a compassionate use program.

By Edward R. Winstead