Date: 2011-04-07
Type of information:
phase: 2
Announcement: results
Company: Roche (Switzerland)
Product: trastuzumab emtansine (T-DM1)
Action mechanism: antibody drug conjugate (ADC). Because a stable linker is used, the ADC largely remains intact outside the cancer cell, with the cytotoxic agent in an inactive state until it enters the cancer cell, thereby minimising exposure of normal cells to the chemotherapy. The humanized monoclonal antibody (trastuzumab) binds to the HER2-positive cancer cells, and is thought to block out of control signals that contribute to cancer growth and survival while also calling on the body’s immune system to attack the cells. After binding, trastuzumab emtansine (T-DM1) is internalized into those cancer cells, DM1 containing metabolites of the conjugate specifically destroy the cells.
Disease: HER2-positive metastatic breast cancer
Therapeutic area: Cancer - Oncology
Country:
Trial details: The TDM4450g Phase II study is a randomized, multicentre international, two-arm, open-label clinical trial including 137 patients with first-line HER2-positive metastatic breast cancer. Patients from approximately 64 sites were randomized to receive either trastuzumab emtansine (T-DM1) or Herceptin® and chemotherapy (docetaxel). The primary endpoints of the study were progression-free survival (PFS) and safety. Secondary endpoints include, objective response, duration of objective response, and clinical benefit rate.
Latest
news: Roche has announced topline results of its first randomized trial of trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer. The Phase II trial, known as TDM4450g, compared trastuzumab emtansine (T-DM1) single agent to the combination of Herceptin® (trastuzumab) and chemotherapy (docetaxel) in previously untreated patients. The results showed that patients treated with trastuzumab emtansine ( T-DM1 ) in this study lived significantly longer with their disease under control (PFS) and experienced fewer side effects typical of chemotherapy.
An earlier analysis of this study presented at the 35th Congress of the European Society of Medical Oncology (ESMO) in 20101 showed encouraging results in tumour shrinkage (overall response rate ORR) in patients with a minimum of 4 months of follow-up. In addition, the study showed that trastuzumab emtansine (T-DM1) significantly reduced the burden of typical side effects associated with conventional chemotherapy.
