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Combination of Tykerb (lapatinib) and Capectabine (Xeloda)

Cancers are uncontrolled growths of abnormal cells. It is not known why they occur. However, some women are more likely to get breast cancer than others.After the cancer spreads, it can form new tumors in other parts of the body. These tumors are called metastases.When cancer spreads, or metastasizes, it travels through either the lymph channels or the bloodstream. By filtering the blood, researchers can identify the cancer cells, called circulating tumor cells, in transit.

They are most often found in the lymph nodes (glands) near the breast. If the cancer spreads through the blood, it most commonly travels to the bones of the pelvis, spine, legs, ribs, and skull. Metastases may also be found in the liver, lungs, and brain.Women with advanced breast cancer who have a higher number of tumor cells circulating in their blood progress more rapidly and die sooner than women with fewer of these cells.Woman whose breast cancer had metastasized, or spread, and who were starting a new treatment had elevated levels of circulating tumor cells in their blood system. Investigators defined an elevated level as five or more tumor cells in a sample of blood.

Metastatic breast cancer may also occur from a recurrence (return) of breast cancer after initial treatment. You may know of only one place where the cancer has spread to. But once there is one site of spread, it is likely that the cancer is growing in other places. The cancer is so small in that area that you don't yet feel any symptoms, and it doesn't show up on X-ray tests. Surgery at this point may not be a good treatment choice for the known area of cancer because it's unlikely to get rid of the whole problem completely. So if you have one or a few metastases, your doctor will probably recommend a whole-body treatment aimed at all the cancer cells in your body.

According to the American Cancer Society, about 180,000 new cases of breast cancer are diagnosed each year. Approximately 8,000 to 10,000 women die from metastatic HER2 positive breast cancer each year. The treatments for metastatic breast cancer include radiation, chemotherapy, and hormone therapies.

You may have just one type of treatment or a combination of treatments. These treatments are not expected to cure metastatic cancer, but they do help to slow down growth of the tumor and decrease its size so that symptoms decrease or disappear.Treatment can sometimes reduce symptoms and extend a patient’s life beyond the general median survival time of 18 to 24 months. Depending on the patient’s disease characteristics, chemotherapy is often recommended as a way to control and slow the cancer’s spread. Such therapy commonly includes a taxane, such as paclitaxel or docetaxel.

Recently,the Food and Drug Administration (FDA) today approved Tykerb (lapatinib), a new targeted anti-cancer treatment, to be used in combination with capectabine (Xeloda), another cancer drug, for patients with advanced, metastatic breast cancer that is HER2 positive (tumors that exhibit HER2 protein). The combination treatment is indicated for women who have received prior therapy with other cancer drugs, including an anthracycline, a taxane, and trastuzumab (Herceptin).

Tykerb, a new molecular entity (NME), is a kinase inhibitor working through multiple pathways (targets) to deprive tumor cells of signals needed to grow. Unlike, for example, trastuzumab — a monoclonal antibody, which is a large protein molecule that targets the part of the HER2 protein on the outside of the cell — Tykerb is a small molecule that enters the cell and blocks the function of this and other proteins. Because of this difference in mechanism of action, Tykerb works in some HER2 positive breast cancers that have been treated with trastuzumab and are no longer benefiting.

"Today's approval is a step forward in making new treatments available for patients who have progression of their breast cancer after treatment with some of the most effective breast cancer therapies available," said Steven Galson, MD, M.P.H., Director of FDA's Center for Drug Evaluation and Research. "New targeted therapies such as Tykerb are helping expand options for patients."

The approval of Tykerb was based on a randomized clinical trial in about 400 women with advanced or metastatic breast cancer that was also HER2 positive. In the trial, half the patients received Tykerb with capecitabine and half received capecitabine alone. Compared to patients receiving capecitabine alone, the group of patients receiving Tykerb with capecitabine had a statistically significant improvement in the time to tumor progression. In addition, the tumor response rate was higher in the group of patients receiving Tykerb with capecitabine (24 percent vs. 14 percent). The survival data are not yet mature.

The most commonly reported Tykerb-related side effects included diarrhea, nausea, vomiting, rash and hand-foot syndrome which may include numbness, tingling, redness, swelling and discomfort of hands and feet. Generally reversible decreases in heart function (that can lead to shortness of breath) have also been reported in a small percentage of patients. Patients should talk to their doctor about potential side effects, potential drug interactions, and other medical conditions including heart and liver problems. Tykerb is available in tablets of 250 mg. An undivided dose of 1,250 mg should be taken orally once daily for 21 days and in combination with capecitabine on days 1-14 of a 21 day cycle.

Tykerb will be distributed by GlaxoSmithKline, of Research Triangle Park, North Carolina.