by ecancer reporter Janet Fricker

A study linking a monoclonal antibody to a cytotoxic drug produced a beneficial effect in patients with HER-2 positive metastatic breast cancer, reported a study at the European Society of Medical Oncology (ESMO), in Milan, Italy, 8-12 October, 2010. The study, reported in the Presidential Symposium, found lower toxicity than for standard therapy.

T-DM1 is the first of a novel type of cancer medicine known as an antibody–drug conjugate that binds together two existing cancer drugs with the aim of delivering both drugs specifically to cancer cells.  Trastuzumab is a monoclonal antibody that targets cells that overproduce the protein HER2 and DM1 is a chemotherapy agent targeting microtubules. “This coupling means that chemotherapy is not found free floating but is delivered inside the cells per se,” said Dr Edith Perez, the principal investigator from the Mayo Clinic (Jacksonville, Florida, USA).

In the phase II open label study,  137 women with HER2-positive recurrent locally advanced breast cancer or metastatic breast cancer, who had no prior chemotherapy for their metastatic disease  were randomised 1:1  to treatment with either trastuzumab plus the chemotherapy drug docetaxel (n=70)  or the new agent T-DM1 (n=67).

Results show that after a median of six months follow-u p investigators found an overall response rate of 47.8% for patients administered T-DM1 versus 41.4% for patients administered trastuzumab and docetaxel. The percentage with clinical benefit (defined as objective response or maintained stable disease for at least six months after treatment) was 55.2% in the T-DM1 group and 57.1% in the trastuzumab plus docetaxel group.

Importantly, T-DMT appears to have a favourable safety profile compared with trastuzumab and docetaxel. The most common adverse events of any grade for T-DM1 and trastuzumab plus docetaxel respectively were alopecia (1.5% versus 66.2%), neutropenia (7.5% versus 57.4%), and diarrhoea (10.4% versus 45.6%).

“This is the first ever presentation of an anti-HER2 antibody-drug conjugate used as first-line therapy for patients with advanced breast cancer. We are encouraged by the results. The study demonstrated that T-DM1 has very good anti-tumour activity as well as much lower toxicity when evaluated side by side with the older standard.”

Fabrice André, from Institut Gustave Roussy in Villejuif, France, commented that the concept   has implications that will go beyond drugs that target HER 2.