What is the ALTTO trial?
Who is eligible to participate in ALTTO?
What is the purpose of the trial?
What treatments are being compared in the ALTTO trial?
How long will the trial last?
Why is lapatinib being studied for early breast cancer?
What side effects are associated with lapatinib?
Who is conducting the ALTTO trial?

ALTTO stands for Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation. The ALTTO trial is an international clinical research study that will evaluate whether the drug lapatinib is effective in helping patients with early breast cancer survive longer after surgery without their cancer returning. It will involve approximately 8,000 patients in 50 countries throughout the world.

Lapatinib is an investigational drug* that works in HER2 (ErbB2)-positive breast cancer, when there is too much HER2 protein in the tumour. Lapatinib has been shown to slow or stop cancer cells from growing and may prevent cancer from returning in patients with HER2-positive, metastatic (advanced) breast cancer. The ALTTO trial aims to investigate if this is also the case in early breast cancer.

The ALTTO trial will enrol patients with HER2 (ErbB2)-positive early breast cancer who have completed surgery. Patients may be eligible to participate in ALTTO if they can answer YES to all  of the following questions:

• Have you been diagnosed with primary breast cancer (also known as early breast cancer)?
• Did you have one lump that was limited to the breast and was removed (or will soon be removed) by surgery?
• Was the tumour tested and found to be HER2 (ErbB2)-positive?
• You also should NOT have had any previous anti-HER2 (ErbB2) therapy, for example, trastuzumab (Herceptin^®) or lapatinib.

There are some additional eligibility criteria that need to be evaluated by the study doctors. For more detailed information on eligibility for the ALTTO trial, go to the Eligibility section (select the button at left). If you think you or someone you know may be eligible to participate in ALTTO, speak to your doctor or contact the trial sponsors (select "Contact information" at left).

Herceptin is a registered trade mark of Genentech, Inc.

The aim of ALTTO is to determine how effective lapatinib is in preventing cancer from returning and in extending survival in patients with HER2 (ErbB2) protein. This study is also being performed for the following additional research purposes:

• To test the safety of lapatinib and to identify what side effects it has
• To find out if the presence of certain substances called biomarkers in breast cancer cells can predict whether lapatinib helps prevent cancer from returning
• To study different reactions to lapatinib based on the genetic differences among different groups of people (called pharmacogenetic research)

The ALTTO trial will compare four treatment options:

• Trastuzumab alone for 52 weeks
• Lapatinib alone for 52 weeks
• Trastuzumab for 12 weeks, followed by a 6-week break, followed by lapatinib for 34 weeks
• Lapatinib in combination with trastuzumab for 52 weeks

Some patients will also be given a chemotherapy drug called taxane weekly during the first 12 weeks of study treatment.

Lapatinib is an oral therapy given once daily in tablet form. Trastuzumab is given intravenously (IV) either weekly or every 3 weeks. Trastuzumab has been shown to be an effective treatment for HER2 (ErbB2)-positive early breast cancer.

This diagram gives an overview of the study treatments.

*Design 1 is now closed to enrollment.

Patients will receive study medication for a total of 1 year (52 weeks) and then will be followed closely by their doctors and the study team. Patients will be followed up for 10 years after the date when they begin taking study medications.

Lapatinib is a new kind of breast cancer treatment that works inside the cell to slow or stop the processes that cause tumour growth and disease progression. Lapatinib is called a targeted therapy because it was specifically designed to interfere with one part of the cell that is responsible for the cancer growth–the HER2 (ErbB2) receptor. Patients who have a tumour that has too much HER2 protein have a greater risk of the disease coming back.

Lapatinib has been shown to be effective in combination with chemotherapy in HER2-positive patients with advanced or metastatic breast cancer that has progressed after treatment with several standard therapies (an anthracycline, a taxane, and trastuzumab).

Because lapatinib has been shown to be effective in some patients with metastatic breast cancer, the investigators of ALTTO believe it may also work in patients with early disease. This trial has been designed to answer that question.

Like all medicines, lapatinib can cause side effects in some, although not all, patients. The following side effects have been seen in cancer patients and healthy volunteers who have taken lapatinib:

Very common side effects (may affect more than 1 in 10 people treated with lapatinib)

• Diarrhoea
• Loss of appetite (anorexia)
• Feeling sick (nausea)
• Being sick (vomiting)
• Rash
• Tiredness (fatigue)

Common side effects (may affect up to 1 in 10 people treated with lapatinib)

• Irregular heartbeat
• Shortness of breath

This research is being conducted by groups of doctors involved in the research and treatment of breast cancer—the Breast International Group (BIG) and the North Central Cancer Treatment Group (NCCTG). This study is also being conducted in collaboration with the pharmaceutical company GlaxoSmithKline (GSK).