My favorite anticancer drug is Tykerb produced by GSK.

It combines the experimental targeted agent lapatinib (Tykerb®) with the drug capecitabine, which delayed the progression of breast cancer for nearly twice as long as did treatment with capecitabine alone in patients with advanced breast cancer that had progressed following treatment with trastuzumab (Herceptin®).

Between 20%-25% of breast cancers overexpresses protein HER2, which is also made by normal breast cells. Tumors that overexpress HER2 (called HER2-positive) tend to grow faster and are more likely to come back than tumors that don’t overexpress the protein.

Since 1998, the drug trastuzumab (Herceptin®) has been used to treat HER2-positive breast cancers that have spread to other organs. Trastuzumab blocks HER2 activity by binding to the part of the protein located on the outside of breast cancer cells. However, many patients with HER2-positive, advanced breast cancer eventually become resistant to trastuzumab therapy, so new treatments are needed.

Lapatinib (Tykerb®) is an experimental drug that, like trastuzumab, blocks the activity of the HER2 protein, but it does so by a different mechanism. Lapatinib binds to the part of the protein found inside breast cancer cells.

A total of 392 patients with advanced, HER2-positive breast cancer were enrolled in this international phase III clinical trial. All of the patients had disease that had begun to progress after treatment with trastuzumab. Patients were randomly assigned to receive either the drug capecitabine alone or capecitabine in combination with lapatinib. Capecitabine is approved by the U.S. Food and Drug Administration to treat breast cancer that has continued to grow despite previous therapy.

Researchers compared the length of time until tumors began to grow again in the two groups of patients. The lead author of the study was Charles E. Geyer, Jr., M.D., of Allegheny General Hospital in Pittsburgh, Pennsylvania.

The study’s results were so compelling that in March 2006 an independent committee monitoring the trial decided to end the trial early and offer patients in the capecitabine-only group the choice of switching to the lapatinib regimen.

At the time the trial was stopped, data were available for 321 of the 392 patients. In patients treated with lapatinib plus capecitabine (161 patients), the median time to disease progression was 8.5 months, compared with 4.5 months for those treated with capecitabine alone (160 patients), a statistically significant finding.

Fewer patients receiving lapatinib had disease recurrence in the brain.Women treated with lapatinib were somewhat more likely to experience mild to moderate diarrhea and “hand-foot syndrome,” a condition characterized by tenderness and sensitivity in the hands and feet. Other side effects were similar in the two groups.

Some patients taking trastuzumab have developed heart problems (HER2 is also made by normal heart and muscle cells.) Consequently, all patients in the current lapatinib study were closely monitored for the development of heart abnormalities. Four of the 161 patients in the lapatinib group developed minor heart problems that reversed when treatment was stopped. No patients withdrew from the study because of heart problems.

Of course there were certain limitations for the drug. Just because the lapatinib regimen delayed disease progression better than capecitabine alone does not mean the combination will actually help patients to live longer. Because the current trial was stopped early for ethical reasons, the follow-up period was too short to be able to measure overall survival differences, Geyer said. He noted that even with longer follow-up it will be difficult to assess if the combined regimen extends survival because many patients in the capecitabine-only group have now switched to combined therapy with lapatinib plus capecitabine.

“Lapatinib with capecitabine is an effective new regimen for advanced HER2-positive breast cancer,” said Geyer. He added that lapatinib and capecitabine should be considered a new standard of care for women with advanced HER2-positive breast cancer who have stopped responding to treatment with trastuzumab. In response to a question from the audience at the ASCO presentation, Geyer noted, however, that lapatinib is still an experimental drug and has not been approved by the U.S. FDA for this or any other indication.

“This is good news,” said Jo Anne Zujewski, M.D., of the National Cancer Institute’s Cancer Therapy Evaluation Program. “Lapatinib is an oral drug that is effective in women who have HER2-positive breast cancer that has progressed following trastuzumab therapy.”
Future clinical trials are planned to directly compare lapatinib to trastuzumab, and to test the value of combining the two drugs. Last year Tykerb has already successfully passed clinical trial phase III. According to GSK researcher, it is highly likely that the drug will be come out to the market soon.

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