TDM1 (Trastuzumab-DM1) Immunoconjugate Drug Therapy Study Open at CORT

A phase III study of Trastuzumab-DM1 for treatment of relapsed her-2 positive metastatic breast cancer is open at CORT. 

Trastuzumab (Herceptin)  is a monoclonal antibody against the her-2 protein, which is overexpressed or amplified in an aggressive subset of breast cancers.  Trastuzumab and chemotherapy combination therapy has substantially improved response, progression-free survival, and overall survival of metastatic her-2 positive breast cancer patients.  Trastuzumab is approved for treatment of metastatic breast cancer.  Trastuzumab may be associated with uncommon infusion reactions and myocardial dysfunction, which may produce clinical congestive heart failure in about 1% of patients, which may be reversible in some cases with discontinuation of therapy.  When her-2 positive metastatic breast cancer progresses on a first-line trastuzumab + chemotherapy regimen, continuing trastuzumab (or another anti-her-2 drug) in the second-line treatment setting (with a different chemotherapy drug) is beneficial with regard to response and stopping disease progression (compared to therapy with chemotherapy alone). 

Lapatinib (Tykerb) is an oral drug that inhibits the intracellular, activating portion of the her-2 molecule.  It has been approved (in combination with capecitabine (Xeloda)) for treatment of metastatic her-2 positive breast cancer that has progressed after trastuzumab-based initial therapy. 

Trastuzumab-DM1 (TDM1) is a drug that combines trastuzumab with a linked chemotherapy agent, maytansine (DM1).   This linkage of an antibody and a drug is termed an immunoconjugate.  The potential advantage of immunoconjugate therapy is that the antibody targets DM1 specifically into tumorous tissue, which may reduce the toxicity of treatment.   In addition, the antibody trastuzumab has it’s own anti-cancer activity.  TDM1 has been tested in open-label phase I and II studies, with mild toxicities and effectiveness, even in heavily pre-treated her-2 positive metastatic breast cancer.  Adverse events that have been noted include elevated liver function tests, fatigue, anemia, and thrombocytopenia. 

The Phase III study at CORT is part of a large multicenter national study.  The study will test the activity of trastuzumab-DM1 versus standard therapy (lapatinib-capecitabine) for second-line therapy of patients with metastatic her-2 positive breast cancer.

For more information about this study, consultation, or referral, contact a CORT Research Coordinator at 972-566-5588, or visit our website at www.CORTPA.com.

Lapatinib (Tykerb) for Treatment of Metastatic Breast Cancer

According to results recently presented at the 2007 annual meeting of the American Society of Clinical Oncology, the targeted agent Tykerb® (lapatinib) may be effective in shrinking cancer that has spread to the brain among some patients with breast cancer.Tykerb is a targeted therapy that has produced promising results in women with metastatic or refractory breast cancer. Targeted therapies are anticancer drugs that are designed to treat cancer cells while reducing damage to normal, healthy cells. Tykerb targets two proteins that often function abnormally in breast cancer cells—HER2 and EGFR. When these proteins are increased in cancer cells (a condition referred to as HER2-positive and/or EGFR-positive cancers), the proteins tend to function abnormally, resulting in uncontrolled, faster growth of cancerous cells. Tykerb decreases or prevents the growth of these cancerous cells.Researchers recently reported results from a clinical study that suggested Tykerb may have anticancer activity among patients with brain metastasis from advanced HER2-positive breast cancer. This study included 241 patients whose brain metastasis continued to progress following therapy with Herceptin® (trastuzumab) and radiation therapy.Nearly half of the patients (46%) experienced at least a 20% reduction in the size of their brain metastasis.An additional 42% of patients achieved stabilization of their disease for at least eight weeks.Overall, 22% of patients had no signs of disease progression within the first six months of treatment with Tykerb.

The most common severe side effects were diarrhea, skin rash, nausea, vomiting, and fatigue.

The researchers concluded that among patients with advanced breast cancer: “Tykerb has promise in the treatment of brain metastases.” Further study of Tykerb in advanced breast cancer is ongoing at CORT. We are conducting a trial of Tykerb with either capecitabine (Xeloda) or topotecan (Hycamptin) chemotherapy for treatment of patients whose brain metastases continue to progress following treatment with Herceptin and radiation therapy.

Tykerb may also increase the activity of other therapies used for HER2-positive metastatic breast cancer patients. Currently, the combination of Herceptin and Taxol (paclitaxel) is a standard-of-care for initial therapy in these patients. CORT is conducting a study that compares that standard treatment of Herceptin and Taxol with or without the addition of Tykerb.

For more information about these studies, visit www.CORTPA.com or contact a Research Coordinator at 972-566-5588.