Roche 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.

“These encouraging data support our ongoing development program for trastuzumab emtansine (T-DM1) in first-line HER2-positive metastatic breast cancer,’’ said Hal Barron, MD, chief medical officer and Head of Global Development. “Trastuzumab emtansine (T-DM1) is a novel treatment with the potential to improve outcomes for patients with HER2-positive breast cancer due to its efficacy and favourable safety profile.”

Data from the TDM4450g study will be submitted for presentation at a future medical congress. 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.

Breast cancer is the most common cancer among women worldwide. Each year about 1.4 million new cases of breast cancer are diagnosed worldwide, and over 450,000 people will die of the disease annually.

In HER2-positive breast cancer, increased quantities of the HER2 receptor are present on the surface of the tumour cells. This is known as ‘HER2 positivity’ and affects approximately 15-25 percent of women with breast cancer.

The TDM4450g phase II study is a randomized, multi-centre 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.
About trastuzumab emtansine (T-DM1)

Trastuzumab emtansine (the generic, or International Non-proprietary Name for T-DM1) is an antibody-drug conjugate (ADC), being studied for HER2-positive metastatic breast cancer. Due to their targeted nature, ADC s allow for the administration of a highly potent, otherwise intolerable , cytotoxic agent.

The ADC largely remains intact outside the cancer cell because a stable linker is used 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.

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