Lapatinib (Tykerb) Fact Sheet

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 an oral  therapy that targets the HER2 protein inside the tumour cell (in a different way to Herceptin®). It is a small molecule and can also enter the central nervous system (i.e. cross the blood brain barrier). Lapatinib represents an effective way of treating advanced or metastatic HER2 positive breast cancer.

Lapatinib is approved for use in combination with an aromatase inhibitor (e.g. letrozole) for the treatment of post-menopausal women with hormone receptor-positive metastatic breast cancer whose tumours overexpress HER2 and for whom hormonal therapy is indicated. The combination has demonstrated a significant improvement in the time before tumour progression.

Clinical trials have also shown that patients with metastatic HER2 positive breast cancer whose disease has progressed despite Herceptin may respond to lapatinib. When combined with the chemotherapy treatment capecitabine (Xeloda®),lapatinib has been shown to delay the progression of advanced disease, almost doubling the time before tumour progression, with  fewer women relapsing with brain metastases.

The potential role of lapatinib in early stage HER2 positive breast cancer will not be known for several years.

For more information on Tykerb®, read the information below or this GlaxoSmithKline brochure on Tykerb.  Any adverse events involving GlaxoSmithKline products should be reported to GSK Medical Information line on 0800 808 500.

1. What is lapatinib?
The trade name for Lapatinib 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 for use in New Zealand:

  •  in combination with an aromatase inhibitor to treat post-menopausal women with hormone receptor-positive breast cancer whose tumours over-express HER2 and for whom hormonal therapy is indicated, or
  •  in combination with capecitabine (Xeloda®) to treat women with advanced or metastatic HER2 positive breast cancer where the tumour has  progressed after treatment with an anthracycline (such as epirubicin or doxorubicin), a taxane (such as docetaxel or paclitaxel) and Herceptin®..

2. Who makes lapatinib?

Lapatinib is manufactured by GlaxoSmithKline under the trade name Tykerb®.

3. How much does it cost?

Some patients in New Zealand may recieve a subsidy for Lapatinib (Tykerb), but others will have to pay for the medication.

Those who have to pay the full cost of the drug will pay around $2300 for a pack of 70 tablets.

However, the drug company GlaxoSmithKline (GSK) has now introduced a programme to limit the total amount individual patients have to pay for Tykerb. The aim is to provide certainty for patients about the maximum cost they will pay for this medication.

Under the new Tykerb Access Programme for Patients (TAPP), those prescribed Tykerb will have to pay for the first 16 packets of the medicine (approximately $37,000).  After this time, GSK will provide any further medication free of charge for as long as the treating physician considers there is continued benefit.

Patients will still have to pay a pharmacist fee of $25 and a courier fee of $10 for packs purchased over and above the first 16 packs. 

You will need to enroll to participate in the TAPP scheme and all prescriptions of Tykerb will be dispensed by the Grafton Pharmacy in Auckland, which will monitor the number of packs distributed.

For further information, including an enrolment form, view the GSK Tykerb information for the consumer.

4. How is lapatinib taken?

Lapatinib tablets are taken once daily and should be taken 1 hour before, or at least 1 hour after food. The number of tablets taken for each dose will vary depending on the reason it is being used. Follow your Doctor’s instructions.
Capecitabine (Xeloda®) and aromatase inhibitors such as letrozole and anastrozole are also taken orally as a tablet.

5. 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, which is a small molecule allowing it to enter the cell, 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®.

6. 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®) and in combination with letrozole (an aromatase inhibitor) to treat advanced HER2 positive breast cancer and works better than either capecitabine or letrozole alone.

7. What are trial results showing for lapatinib?

In a Phase III trial of post-menopausal women who had not received prior treatment for their advanced breast cancer and whose tumours were both hormone-receptor positive and HER2 positive, the combination of Tykerb plus letrozole in 111 women resulted in a median progression free survival of 8.2 months as compared to 3.0 months for the 108 women receiving letrozole alone.

Tykerb plus letrozole is an oral, chemotherapy-free drug combination and may be considered as a first-line treatment option for appropriate patients with advanced breast cancer.

Findings from the trial of lapatinib and letrozole were reported in the November 20 2009 issue of Journal of Clinical Oncology. SOURCES  Johnston, S. .J Clin Oncol Nov 20, 2009, vol 27: pp 5538-5546.  You can read this scientific article here.

In another Phase III trial Tykerb was combined with capecitabine (Xeloda®) in a more heavily pre-treated group of patients with advanced breast cancer. These 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 tablets alone or lapatinib tablets in combination with capecitabine tablets.. 392 patients with advanced HER2 positive breast cancer were enrolled in this trial. 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 8.4 months compared with 4.4 months for those treated with capecitabine alone.

Findings from the trial 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. The final survival analysis was published in Oct 2010. SOURCES: Cameron, D. The Oncologist, 2010: vol 15, pp 924-934.

8. 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.

9. 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 registered and approved for use in New Zealand. It is, however, not funded by PHARMAC which means patients will have to pay to have this drug.The price may vary from pharmacy to pharmacy. You may wish to discuss this with your pharmacist. Lapatanib can be prescribed by a NZ doctor but patients treated are not covered by ACC in the event of an adverse reaction.

10. Should I be taking it?

At this stage, Herceptin® remains the gold standard treatment for the majority of women with previous untreated metastatic HER2 positive breast cancer.  Tykerb in combination with letrozole may be an option in appropriate patients where an oral chemo-therapy free treatment option is desired. There is no information yet on lapatinib in early breast cancer, but clinical trials are underway.

11. Can lapatinib be used to treat inflammatory breast cancer?

Lapatinib is not approved for use in inflammatory breast cancer in New Zealand.