Lapatinib (Tykerb) Fact Sheet

1. What is lapatinib?
2. Who makes lapatinib?
3. How is lapatinib taken?
4. How does it work?
5. How is it used?
6. What are trial results showing for lapatinib?
7. Is lapatinib toxic to the heart?
8. What are the side effects?
9. Is lapatinib available and what does it cost?
10. Should I be taking it?
11. Can lapatinib be used to treat inflammatory breast cancer?

Some Background on lapatinib (Tykerb®).

Normal breast cells produce a protein called HER2, but some breast cancer cells can make too much (overexpress) of it. These HER2 positive breast cancers tend to grow faster and are more likely to recur than tumours that do not over express this protein.

Since 1998, Herceptin (trastuzumab) has been used to successfully treat HER2 positive breast cancers that have spread beyond the breast and the lymph nodes under the arm to other organs within the body (advanced or metastatic breast cancer). However, in the majority of patients with advanced HER2 positive breast cancer, the disease will eventually progress despite Herceptin treatment. In some cases, the cancer will spread to the brain probably because Herceptin and other chemotherapy regimens cannot adequately cross the blood-brain barrier. These problems highlight the need for new drug treatments.

Lapatinib is a new oral therapy that targets the HER2 protein. Clinical trials have shown that patients with metastatic HER2 positive breast cancer whose disease has progressed despite Herceptin may respond to lapatinib. This represents a new and effective way of treating advanced HER2 positive breast cancer. Lapatinib can enter the central nervous system (i.e. cross the blood brain barrier) and, when partnered with the chemotherapy treatment capecitabine (Xeloda), is proving to be successful in delaying the progression of advanced disease, almost doubling the time before tumour progression and fewer women are relapsing with brain metastases. The potential role of lapatinib in early stage HER2 positive breast cancer will not be known for several years.

Two clinical trials testing the effectiveness of lapatinib in early HER2 positive breast cancer are scheduled to begin in New Zealand in 2007.

1. What is lapatinib? Lapatinib’s trade name is Tykerb. Like Herceptin, lapatinib is a targeted therapy for treating HER2 positive breast cancer. 20-25% of breast cancer patients are HER2 positive. Lapatinib is currently approved by the Food and Drug Administration (FDA) in the USA to treat women with advanced or metastatic HER2 positive breast cancer in combination with capecitabine (Xeloda).

2. Who makes lapatinib? Lapatinib is manufactured by GlaxoSmithKline under the trade name Tykerb.

3. How is lapatinib taken? Both lapatinib and capecitabine are taken orally as a pill.

4. How does it work? HER2 positive breast cancers make too much of the HER2 protein. Herceptin blocks the activity of the HER2 protein on the outside surface of a breast cancer cell while lapatinib binds to the HER2 protein component inside the cell. Because of this difference, lapatinib represents an alternative way of blocking the HER2 pathway. It also blocks the HER1 pathway, so may cause a more complete blockage. These two differences mean it may work when cancers have become resistant to Herceptin. 

5. How is it used? Lapatinib can be used alone to treat advanced HER2 positive breast cancer that has progressed on Herceptin, however the chance of a response is low. Lapatinib has been studied in combination with capecitabine (Xeloda) to treat advanced HER2 positive breast cancer and works better than capecitabine alone.

6. What are trial results showing for lapatinib? Results from a phase III clinical trial were announced at the American Society of Clinical Oncology annual meeting in Atlanta, Georgia on June 3 2006. 392 patients with advanced HER2 positive breast cancer were enrolled in this trial. All patients had disease that had begun to progress after treatment with Herceptin and anthracycline based chemotherapy (i.e. doxorubicin/Adriamycin or epirubicin) and taxanes (paclitaxel/Taxol or docetaxel/Taxotere). Patients were randomly assigned to receive either capecitabine alone or lapatinib in combination with capecitabine. Researchers compared the length of time until tumours began to grow again in the two groups. In the group that received lapatinib and capecitabine, the median time until the disease began to progress was 8.5 months compared with 4.5 months for those treated with capecitabine alone.

Findings from the trials of lapatinib and capecitabine appear in the Dec. 28 2006 issue of the New England Journal of Medicine. SOURCES: Geyer, C.E. The New England Journal of Medicine, Dec. 28, 2006; vol 355: pp 2733-2743.

7. Is lapatinib toxic to the heart? HER2 protein is also present on the surface of heart muscle. Lapatinib can affect heart muscle function. It may cause less toxicity to the heart (i.e. weakening of the heart muscle) than Herceptin, but this is still being studied. Caution should be taken if lapatinib is being considered for patients with pre-existing cardiac conditions, including uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure.

8. What are the side effects? The most common side effects of lapatinib with capecitabine are diarrhoea, redness and tingling in the hands and feet and a rash and lowering of blood counts. These side-effects (except the rash) are also the most common side-effects of capecitabine alone. They can usually be successfully treated. Other effects can include nausea, vomiting and fatigue. The most common side effects of lapatinib alone are diarrhoea, rash and fatigue.

9. Is lapatinib available and what does it cost? Lapatinib is Medsafe registered and approved for use in New Zealand. It is, however, not funded by PHARMAC. Lapatanib can be prescribed by a NZ doctor but patients so treated are not covered by ACC in the event of an adverse reaction. It is likely to cost somewhat more than Herceptin, but there is no infusion cost.

10. Should I be taking it? At this stage, Herceptin remains the gold standard treatment for women with previous untreated metastatic HER2 positive breast cancer. There is no information yet on lapatinib in early breast cancer, but clinical trials are underway and soon to start in NZ. Discuss with your medical oncologists the lapatinib studies available at your hospital.

11. Can lapatinib be used to treat inflammatory breast cancer? Results from a Phase 2 study of 35 patients were presented at the 29th Annual San Antonio Breast Cancer Symposium (SABC) by Massimo Cristofanilli MD from the University of Texas MD Anderson Center in Houston (December 14 2006). These results indicated that lapatinib showed activity in patients with newly diagnosed inflammatory breast cancer (IBC) both alone and when used in combination with paclitaxel. These results are promising.