KADCYLA APPROVED BY EMA

Trastuzumab emtansine (Kadcyla, Roche/ImmunoGen) has now been approved in Europe for use in the treatment of HER2-positive metastatic breast cancer, following a positive opinionissued in September.

The product was approved in the United States in February, and was approved in Japan in September.

The novel product is comprised of the HER2-targeting monoclonal antibody trastuzumab linked to the cytotoxic agent DM1 (the product is also known as T-DM1). It is approved for use in patients with HER2-positive metastatic breast cancer who were previously treated with trastuzumab (Herceptin, Genentech/Roche) and a taxane chemotherapy, separately or in combination.

This indication is based on results from the pivotal phase 3EMILIA study, which involved 991 patients and showed a significantly improved overall survival for those on the novel drug. Patients on trastuzumab emtansine survived nearly 6 months longer than patients receiving the standard therapy of lapatinib (Tykerb) plus capecitabine (Xeloda) (median overall survival, 30.9 vs 25.1 months), and also experienced fewer severe adverse (reported by 43.1% vs 59.2% with standard therapy).

In the press release announcing the European Union approval, Roche gave further details about the adverse events reported as follows. The most common grade 3 or higher adverse events reported in patients receiving trastuzumab emtansine were thrombocytopenia (12.9%), elevated AST (4.3%), elevated ALT (2.9%), anemia (2.7%), fatigue (2.4%), hypokalemia (2.2%), and neutropenia (2%). For patients receiving lapatinib and capecitabine, they were diarrhea (20.7%), hand and foot syndrome (16.4%), vomiting (4.5%), neutropenia (4.1%), fatigue (3.5%), nausea (2.5%), and mucosal inflammation (2.3%).

When the EMILIA trial results were first reported, breast cancer experts were enthusiastic about both the survival advantage and the reduced adverse events. Kathy Miller, MD, associate professor of medicine at Indiana University School of Medicine in Indianapolis, said in her Medscape videoblog: "This is the classic light-beer scenario: It's less filling and tastes great. T-DM1 was more effective by every measure: improvement in overall response rate, disease-free survival, progression-free survival, overall survival, and less toxicity. It was a clear winner if ever there was one."

However, after the product was launched, there was frustration about its high price tag. This product is the third HER2-targeted therapy from the Roche/Genentech stable. The original targeted drug trastuzumab (Herceptin) was launched 1988, and in the United States costs around $4500 per month, then in 2012 came pertuzumab (Perjeta), which costs around $6000 per month, and now there is trastuzumab emtansine, which costs around $9800 per month.