A drug antibody conjugate called ado-trastuzumab emtansine (Kadcyla) received FDA approval Friday for HER2-positive, metastatic breast cancer.
The new therapy is intended for use in patients who have already undergone unsuccessful treatment with trastuzumab (Herceptin) and a taxane. The trastuzumab portion of the conjugate -- called T-DM1 during clinical development -- targets HER2-positive cells, at which point the attached chemotherapeutic molecule -- DM1 -- attacks the cancer cells.
“This provides a significant leap to a whole other group of drugs, not only for HER2 because this adds a new drug for people who’ve already seen their tumor grow through trastuzumab as well as some of the other antibodies such as pertuzumab or … the tyrosine kinase inhibitors such as lapatinib,†Jennifer Litton, MD, of the University of Texas MD Anderson Cancer Center in Houston, told 鶹ý.
Ado-trastuzumab emtansine becomes that fourth approved therapy targeting the HER2 protein, following trastuzumab, lapatinib (Tykerb), and pertuzumab (Perjeta). Lapatinib is marketed by GlaxoSmithKline, and the other three therapies are marketed by Genentech.
The approval was based on the EMILIA study, which involved patients with HER2-positive, metastatic breast cancer who had failed treatment with trastuzumab and a taxane. They were randomized to ado-trastuzumab emtansine or conventional therapy with lapatinib and capecitabine (Xeloda).
According to final results reported in October, ado-trastuzumab emtansine resulted in significant improvements in both co-primary endpoints -- progression-free survival (9.6 versus 6.4 months) and overall survival (30.9 versus 25.1 months). Several secondary outcomes improved, as well.
Although adverse events at grades 3 or 4 were less frequent with the new therapy in the trial (41% versus 57%), it is not without risk.
The drug's label will contain a boxed warning advising patients and healthcare professionals about risks of liver toxicity, reductions in left ventricular ejection fraction, and death. In addition, the boxed warning will detail risks of severe birth defects, so a woman's pregnancy status should be determined before starting treatment, the FDA said.
The most common side effects associated with the drug are nausea, fatigue, musculoskeletal pain, thrombocytopenia, elevated transaminases, headache, and constipation.
UPDATE: This article, originally published on Feb. 22, 2013 at 10:55 a.m., was updated with new material at 2:40 p.m.