Massachusetts General Hospital Cancer Centre and GlaxoSmithKline (GSK), has announced the initiation of a landmark international breast cancer clinical trial, TEACH (Tykerb Evaluation After CHemotherapy).
This will be the first phase III study to investigate whether adjuvant treatment with lapatinib will improve disease-free survival in women with early-stage HER2 (ErbB2)-positive breast cancer, including those with positive and negative node involvement. An adjuvant therapy is one that is administered in addition to primary surgical or radiation treatment to lower risk of disease progression.
Approximately 3,000 women will be enrolled from more than 450 centres in more than 30 countries. Lapatinib is an investigational drug that is not marketed for any indication in any country at this time.
"The initiation of this trial represents another step toward understanding the role of targeted therapies in extending disease-free survival," said Dr Paul Goss, director of breast cancer research, Massachusetts General Hospital Cancer Centre, who proposed the Teach study and will chair the International Steering Committee. "Women who have HER2-positive breast cancer are at a high risk of the disease returning, which is of great concern to patients and physicians. The landmark Teach study will be the first to investigate the use of a dual EGFR and HER2 inhibitor as an adjuvant treatment for women with HER2-positive breast cancer."
Between 20 per cent and 30 per cent of human breast cancers over express HER2. Because of the distinct clinical features of HER2-positive breast cancer, women have a high risk of disease recurrence and thus, poorer prognosis.
In current clinical practice trastuzumab is now becoming part of standard adjuvant therapy together with chemotherapy. However, many thousands of women with HER2-positive cancer have already received adjuvant therapy without trastuzumab. Although these patients remain at elevated risk of relapse, there is no data to support initiating additional trastuzumab treatment in patients who did not receive trastuzumab within seven weeks of completing their adjuvant therapy. In addition, trastuzumab is not licensed for use in all countries.
"Researchers are continually seeking ways to stay one step ahead of cancer. We must be proactive with treatments for women who have a distinctive disease prognosis - those with HER2-positive breast cancer," said Paolo Paoletti, MD, senior vice president of the Oncology Medicine Development Centre at GSK. "GlaxoSmithKline is excited that lapatinib will be used in the first study that will investigate the use of a dual EGFR and HER2 inhibitor as an adjuvant treatment for these women - the Teach trial."
Lapatinib is a dual kinase inhibitor that potently blocks the action of both EGFR (ErbB1) and HER2 receptors within the cancer cell, which are associated with cell proliferation and tumour growth. A small molecule tyrosine kinase inhibitor once-daily oral medication, lapatinib is currently in late-stage clinical development for the treatment of patients with advanced metastatic breast cancer and in earlier phases of investigation for treatment of a range of other solid tumours.
In a phase III study of lapatinib in combination with capecitabine in patients who have progressed on Herceptin, an Independent Data Monitoring Committee due to positive results stopped treatment early. The registration file is currently under review by regulatory authorities in US and various EU/International countries.
The Teach trial will be conducted at approximately 450 clinical research sites globally and approximately 3,000 women will be enrolled. The study is designed to compare the efficacy and safety of lapatinib versus placebo in women treated for early-stage, HER2-positive breast cancer who have no clinical or radiographic evidence of disease.