A planned interim review of early data from ALTTO—a phase III, four-arm study of adjuvant lapatinib (Tykerb®/Tyverb®), trastuzumab, their sequence and their combination in patients with HER2 (ErbB2)-positive, early-stage breast cancer—has resulted in a change to the ongoing study. The independent data monitoring committee that carried out the review has recommended that three of the trial arms continue without modification. However, the committee has indicated that the lapatinib alone arm is unlikely to meet the pre-specified criteria to demonstrate non-inferiority to trastuzumab alone with respect to disease-free survival. Consequent to this finding, patients assigned to the lapatinib alone arm of the trial will discontinue lapatinib and discuss treatment options with their study physician.This study is fully recruited and the remaining three arms of the trial will continue as planned.
Use of lapatinib in an adjuvant setting is not approved anywhere in the world.
For patients who have been enrolled in the ALTTO trial, please contact your doctor.
Trial Overview
What is 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 8400 patients in 50 countries throughout the world.

The ALTTO trial aims to investigate whether lapatinib helps prevent cancer from returning in early breast cancer. Lapatinib is not approved for doctors to prescribe to patients with HER2 (ErbB2)-positive early stage breast cancer.
Who is eligible to participate in ALTTO?
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 at least 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.
What treatments are being compared in the ALTTO trial?
The ALTTO trial will compare four treatment groups:

  • Trastuzumab alone for 52 weeks
  • Lapatinib alone for 52 weeks
  • Trastuzumab for 12 or 18 weeks, followed by a 6-week break, followed by lapatinib for 28 or 34 weeks
  • Lapatinib in combination with trastuzumab for 52 weeks

Patients will be given chemotherapy during the first 12 or 18 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.

The diagrams below give an overview of the study designs and treatments.

Design 1*: All (neo)adjuvant chemotherapy is completed prior to study treatments.


*Design 1 is now closed to enrollment.

Design 2: A taxane is given concurrently with study treatments.




Design 2 is now closed to screening.

Design 2B: Nonanthracycline regimen containing docetaxel and carboplatin given concurrently with study treatments.


Available in North America only for new patient enrollment.

Study treatment will be administered for 1 year (52 weeks); patients will be followed for a total of 10 years.
What is the purpose of the trial?
The purpose of this study is to evaluate the safety of the study treatments and determine how well they work in early stage HER2-positive breast cancer.
How long will the ALTTO trial last?
Patients will receive study medication for a total of 1 year (52 weeks) and 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.
Why is lapatinib being studied for early breast cancer?
The ALTTO trial is designed to see whether lapatinib may work in patients with early breast cancer (when the tumour has not spread beyond the place where it started).
What side effects are associated with lapatinib?
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)

  • Diarrhea (which may make you dehydrated)
  • 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)

  • Poor heart function, which most people do not notice. But a small number of patients (less than 1%) may feel an irregular heartbeat or shortness of breath
  • Nail disorders, such as tender infection and swelling of the cuticles

Uncommon side effects (may affect up to 1 in 100 people treated with lapatinib):

  • Drug-induced lung inflammation, which may cause shortness of breath or cough. These symptoms may persist after you stop taking lapatinib
  • Liver problems which may cause itching, yellow eyes or skin, dark urine, pain or discomfort in the right upper area of the belly (tummy, stomach)

Severe allergic reaction (may affect up to 1 in 1000 people treated with lapatinib):

This rare side effect develops rapidly. Symptoms may include:

  • Skin rash (including itchy, bumpy rash)
  • Unusual wheezing, or difficulty in breathing
  • Swollen eyelids, lips, or tongue
  • Pains in muscles or joints
  • Collapse or blackout
What side effects are associated with trastuzumab?
Very common side effects (may affect more than 2 in 10 people treated with trastuzumab):

  • Body pain (muscles, joints, and abdomen)
  • Headache
  • Weakness
  • Tiredness (fatigue)
  • Fever
  • Chills
  • Feeling sick to your stomach (nausea)
  • Being sick to your stomach (vomiting)
  • Diarrhea (which could lead to dehydration)
  • Shortness of breath and/or cough

Common side effects (may affect up to 2 in 10 people treated with trastuzumab):

  • Rash
  • Infection
  • Swelling of feet and ankles
  • Low blood cell counts (may feel tired or weak, may have more risk of infection)
  • Trouble sleeping
  • Dizziness
  • Depression (feeling down or blue)
  • Voice changes (hoarseness)
  • Runny nose and/or sore throat
  • Loss of appetite (anorexia)
  • Skin tingling or numbness

Uncommon side effects

Serious side effects of trastuzumab that may or may not be related to the drug, but which have been seen in less than 2 to 3 in 100 people receiving trastuzumab:

  • Allergic reaction (including life-threatening low blood pressure, shortness of breath and death)
  • Damage to the heart (including abnormal rhythms, damage to the heart muscle)
  • Neuropathy (numbness, tingling, or other nerve problems, usually in hands and feet)
  • Interstitial pneumonitis—inflammation (swelling) in the lungs (may have trouble breathing)
  • Liver problems (as seen in a blood test)

Trastuzumab contains benzyl alcohol, a preservative that is known to cause side effects in newborns. This drug should not be given to anyone with a known allergy or sensitivity to benzyl alcohol.
Are there other risks associated with the ALTTO trial?
Yes, there are additional risks involved with participating in the ALTTO trial. Please contact your doctor to discuss these risks.
Who is conducting the ALTTO trial?
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).
                 

Copyright © 2012 GlaxoSmithKline Group of Companies
All rights reserved.