Breast Cancer Study Establishes New Model for Global Clinical Trials

Two targeted agents designed to treat HER2-positive 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. The ALTTO trial (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization), 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 US-based Breast Cancer Intergroup of North America (TBCI) and the Belgium-based Breast International Group (BIG).

The randomized, phase III ­ALTTO investigation is designed to answer the several pressing questions regarding two widely used cancer agents, trastuzu­mab (Herceptin) and lapatinib (Tykerb): 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?

Two Different Designs

The trial is unusual in that it has two different designs depending on whether patients with stage I or 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.

"There have been major improvements in the management of patients with early breast cancer in the last few years, so this new study builds on this knowledge and sets an example of the new era: good science, good worldwide collaboration," said Edith Perez, md, an oncologist in the North Central Cancer Treatment Group at Mayo Clinic in Jacksonville, Fla, who will lead the study for TBCI. "It may be that using two treatments that work in different ways against HER2-positive breast cancer offers a complementary strategy that is more powerful than either drug alone."

Collection of Biologic Material

ALTTO will be one of the first trials of its scope in which translational research plays a critical role, investigators say. In ALTTO, biologic material will be collected from thousands of patients in order to determine a tumor profile that responds best to the drugs-information that could lead to individualized patient care and, possibly, to development of next-generation agents.

"The difference between this study and many that came before it is that the collection of biological materials occurs as the trial is being conducted, not as an afterthought. While there are exceptions, not many companies or organizations have been willing to invest in that kind of research before," said Martine J. Piccart, md, phd, professor of oncology at the Universit Libre de Bruxelles, Belgium, and lead investigator for BIG, which she founded in 1996. "Now we have the chance to optimize therapy with powerful drugs in order to provide the best treatment possible for each of our patients."

Perez and Piccart led the development team of the ALTTO trial and will act as the study's co-principal investigators. To date, more than 300 centers around the world have enrolled patients into ALTTO. Full enrollment is expected to involve about 500 centers in the United States and more than 800 centers in Europe and the rest of the world. A complete listing of ALTTO participating sites can be found by searching for ALTTO at http://clinicaltrials.gov.