The U.S. Food and Drug Administration (FDA) has approved trastuzumab emtansine, or T-DM1, for the treatment of people with HER2-positive metastatic breast cancer (mBC) who have received prior treatment with trastuzumab and a taxane chemotherapy.

An antibody-drug conjugate (ADC) is a new kind of targeted cancer medicine that can attach to certain types of cancer cells and deliver chemotherapy directly to them. Trastuzumab emtansine is the first FDA-approved ADC for treating HER2-positive mBC, an aggressive form of the disease.

“(Trastuzumab emtansine) is an antibody-drug conjugate representing a completely new way to treat HER2-positive metastatic breast cancer, and it helped people in the EMILIA study live nearly six months longer,” said Hal Barron, M.D., Roche’s Chief Medical Officer and Head, Global Product Development. “We currently have more than 25 antibody-drug conjugates in our pipeline and hope this promising approach will help us deliver more medicines to fight other cancers in the future.”

Trastuzumab emtansine is made up of the antibody, trastuzumab, and the chemotherapy, DM1, joined together using a stable linker. It combines the mechanisms of action of both trastuzumab and DM1, and it is the first Roche ADC approved by the FDA. Roche has studied ADC science for more than a decade and has eight ADCs in Phase I or Phase II studies for different types of cancer.

Roche has also submitted a Marketing Authorisation Application to other Regulatory Authorities around the world, including the European Medicines Agency (EMA), for trastuzumab emtansine for the treatment of people with HER2-positive mBC. This application is currently under review by the EMA.

The FDA approval of trastuzumab emtansine is based on results from EMILIA (TDM4370g/BO21977), an international, Phase III, randomised, open-label study comparing Kadcyla alone to lapatinib in combination with Xeloda (capecitabine) in 991 people with HER2-positive locally advanced breast cancer or mBC who had previously been treated with Herceptin and a taxane chemotherapy.

Results include:

• The study met both co-primary efficacy endpoints of overall survival and progression-free survival (PFS; as assessed by an independent review committee).
• People who received trastuzumab emtansine lived a median of 5.8 months longer (overall survival) than those who received the combination of lapatinib and Xeloda, the standard of care in this setting (median overall survival: 30.9 months vs. 25.1 months).
• People receiving Trastuzumab emtansine experienced a 32 percent reduction in the risk of dying compared to people who received lapatinib and Xeloda (HR=0.68; p=0.0006).
• People who received trastuzumab emtansine lived significantly longer without their disease getting worse (PFS) compared to those who received lapatinib plus Xeloda (HR=0.65, 35 percent reduction in the risk of disease worsening or death, p<0.0001; median PFS 9.6 months vs. 6.4 months).
• No new safety signals were observed and adverse events (AEs) were consistent with those seen in previous studies, with fewer people who received Kadcyla experiencing Grade 3 or higher (severe) AEs than those who received lapatinib plus Xeloda (43.1 percent vs. 59.2 percent).
• For people receiving Trastuzumab emtansine, the most common (occurring in more than 2 percent of participants) Grade 3 or higher AEs were low platelet count (14.5 percent), increased levels of enzymes released by the liver and other organs (8.0 percent), low red blood cell count (4.1 percent), low levels of potassium in the blood (2.7percent), nerve problems (2.2percent) and tiredness (2.5percent)

Source: Roche