Kadsila against breast cancer

A new personalized medicine drug for the treatment of breast cancer has been approved

"Moscow pharmacies" based on the materials of the Rosh press release

Roche announced that the U.S. Food and Drug Administration (FDA) has approved the use of the drug Kadsil (trastuzumab emtanzine or T-DM1) for the treatment of patients with HER2-positive metastatic breast cancer (MMC), previously treated with Herceptin (trastuzumab) and chemotherapy with taxanes. Kadsila has become the fourth Roche drug for the treatment of patients with advanced stages of malignant neoplasms that has received FDA approval over the past two years.

Antibody and chemotherapy drug conjugates are a new group of targeted drugs. Conjugates bind to tumor cells and provide delivery of the chemotherapy drug directly into the cell. Kadsila became the first drug from the conjugate group to receive FDA approval for the treatment of patients with HER2-positive metastatic breast cancer (MMC) – a particularly aggressive form of breast cancer.

"Kadsila, an antibody and drug conjugate, is a completely new way to treat HER2–positive metastatic breast cancer. The use of this drug in the EMILIA study made it possible to extend the life of patients by almost six months," said Hal Barron, MD, chief medical officer and head of the global drug development division of Roche. "We currently have more than 25 antibody–drug conjugates in development, and we hope that in the future this promising approach will allow us to produce even more drugs to fight various forms of cancer."

Kadsil consists of the trastuzumab antibody and the DM1 chemotherapy drug, which are linked by a stable linker. Kadsila combines the mechanisms of action of trastuzumab and DM1 and is the first of the antibody and chemotherapy drug conjugates developed by Roche, which is approved for use by the FDA. Roche has been researching such drugs for more than ten years. Clinical studies of the first or second phase are being conducted on the use of eight conjugates for various malignant neoplasms. Roche has submitted applications for registration of the use of Cadsila for the treatment of HER2-positive breast cancer to regulatory authorities around the world, including the European Medicines Agency (EMA). The agency is currently reviewing this testimony.

The effectiveness of Kadsil in the therapy of HER2-positive breast cancer

The FDA approval of the use of Kadsil is based on the results of an international, randomized, open-label phase III study of EMILIA (TDM4370g/BO21977), in which Kadsil, used in monotherapy mode, was compared with lapatinib in combination with Xeloda (capecitabine) in 991 patients with HER2-positive locally advanced breast cancer or breast cancer, previously treated with Herceptin (trastuzumab) and chemotherapy with taxanes.

The main results of the study:

• The study reached both endpoints of effectiveness evaluation – an increase in overall survival and disease progression-free survival (IBD, according to an independent monitoring committee).
• Patients receiving Kadsila lived an average of 5.8 months longer (overall survival) than those who received standard treatment for this form of the disease – a combination of drugs lapatinib and Xeloda, (median overall survival: 30.9 months and 25.1 months, respectively).
• The study demonstrated a 32% reduction in the risk of death in patients receiving Kadsila compared to those who received a combination of lapatinib and Xeloda (HR=0.68; p=0.0006).
• Cadsila-treated patients achieved a significant increase in the duration of the period during which they lived without disease progression (IBD), compared with those who received lapatinib and Xeloda (HR=0.65, reduced risk of disease progression or death was 35%, p<0.0001; median IBD was 9.6 months and 6.4 months, respectively).
• In the course of the study, no new manifestations of toxicity were observed, while adverse events (NS) corresponded to the phenomena observed in previous studies. In patients treated with Kadsil, adverse events of the third degree of severity (severe) and higher were observed less frequently than in those who received lapatinib and Xeloda (43.1% and 59.2%, respectively).
• Among the adverse events of 3 degrees of severity and higher (in more than 2% of patients) in the group of patients receiving Kadsila, there were: a decrease in the number of platelets (14.5%), an increased level of enzymes (including liver enzymes) (8.0%), a decrease in the number of red blood cells (4.1%), a low level of potassium in the blood (2.7%), disorders of the nervous system (2.2%) and fatigue (2.5%).

About the drug Kadsil

Kadsil is a conjugate of an antibody and a chemotherapy drug (ADC). Currently, Kadsila is being investigated in the treatment of HER2-positive malignant tumors. This is the first conjugate that appeared as a result of 30 years of research on the HER2 signaling pathway by Roche and Genentech, and the third drug developed by Roche for the treatment of HER2-positive breast cancer. Like Herceptin, Kadsila binds to HER2-positive cells. It is believed that Kadsil blocks signaling pathways, the activation of which leads to tumor growth, and also stimulates the immune system to attack cancer cells. Inside malignant cells, the effect of the drug trastuzumab emtanzine is aimed at their destruction by releasing DM1. The company Roche, patented the technology of synthesis and production of the drug Kadsil under an agreement with ImmunoGen, Inc.

Portal "Eternal youth" http://vechnayamolodost.ru04.03.2013