New study of targeted therapies for breast cancer -- model for global clinical trials

Two targeted medications designed to treat an aggressive form of breast cancer are being tested in a new study involving 8,000 participants in 50 countries across six continents -- a clinical trial that investigators hope will provide a new model for global cancer research. This trial, dubbed ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization study), will be one of the first global initiatives in which two large, academic breast cancer research networks covering different parts of the world have jointly developed a study in which all care and data collection are standardized, regardless of where patients are treated. The networks are The Breast Cancer Intergroup of North America (TBCI), based in the United States, and the Breast International Group (BIG) in Brussels, Belgium. TBCI consists of six National Cancer Institute (NCI)-funded clinical trials cooperative groups. NCI is part of the National Institutes of Health.

ALTTO is designed to answer the most pressing questions regarding use of two widely used cancer agents: whether one agent is more effective, which agent is safer for patients, and what benefit will be derived by taking the drugs separately, in tandem order, or together" The trial is a randomized, Phase III study, which is considered a gold standard method for proving drug effectiveness.

The two agents tested in ALTTO are drugs designed to treat HER2-positive tumors, which is a particularly aggressive form of cancer that affects approximately 20 percent to 25 percent of breast cancer patients. Both agents, trastuzumab (Herceptin) and lapatinib (Tykerb), have already been approved by the U.S. Food and Drug Administration for use for treatment of HER2-positive breast cancer. ALTTO will provide the first head-to-head comparison of trastuzumab and lapatinib in the earliest, most treatable stages of cancer. It will also be one of the first large-scale studies to evaluate lapatinib’s effectiveness in treating early breast cancer.

HER2-positive breast cancer is caused by an excess of HER2 genes or by over-production of its protein, the HER2 cell surface receptor. Trastuzumab consists of large antibodies that once injected into patients, latch on to the portion of the HER2 protein that sits on the outer surface of the cancer cell whereas lapatinib acts by entering a cancer cell and binding to the part of the HER2 protein that lies beneath the surface of the cell.

The trial is unusual in that it has two different designs depending on whether patients with stage I or stage II breast cancer have already been treated with chemotherapy. The study thus will compare four different regimens of targeted therapy administered over a 52-week period. Patients will be randomized to receive either trastuzumab or lapatinib alone, or trastuzumab followed by lapatinib, or the two treatments in combination.