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.