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F.D.A. Approves a New Roche Drug for Advanced Breast Cancer
 
 
  F.D.A. Approves a New Roche Drug for Advanced Breast Cancer MedPageToday:
 
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 MedPage Today.
 
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.
 
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NY Times By ANDREW POLLACK
Published: February 22, 2013
 

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The Food and Drug Administration on Friday approved a new type of drug that combines the widely used breast cancer medicine Herceptin with a powerful toxin to more effectively kill cancer cells while potentially reducing side effects.
 
Kadcyla, which was known as T-DM1 during its development by Genentech, extended the median survival of women with advanced breast cancer by nearly half a year in a clinical trial.
 
The drug, which will be called Kadcyla but was known as T-DM1 during its development, extended the median survival of women with advanced breast cancer by nearly half a year in a clinical trial.
 
Genentech, which developed the drug, said it would cost about $9,800 a month, or $94,000 for a typical course of treatment. That is about twice the price of Herceptin itself, which is also made by Genentech, but it is similar to the price of some other new cancer drugs.
 
Kadcyla, which the company said could be available within days, is one of the first successful examples of a new class of drugs that link toxins to proteins known as monoclonal antibodies. The antibodies latch onto tumors and deliver the toxic payload. Because the toxin is not activated until it reaches the tumor, healthy cells are spared and some side effects are avoided.
 
Such medicines, known as antibody-drug conjugates, are a hot area for cancer drug developers, with around two dozen such drugs in clinical trials. Another antibody-drug conjugate, Adcetris, developed by Seattle Genetics, was approved in 2011 as a treatment for two rare types of lymphoma.
 
The linker and toxin used in Kadcyla were developed by ImmunoGen, based in Waltham, Mass., which will receive royalties on sales of the drug. This is the first approved product for ImmunoGen, which has been working on antibody-drug conjugates for three decades.
 
The main clinical trial leading to approval of Kadcyla involved 991 patients with metastatic breast cancer that was worsening despite treatment with Herceptin and a taxane chemotherapy drug, like paclitaxel. Half the women were given infusions of Kadcyla and the other half took two pills now commonly used for such patients: Tykerb, also known as lapatinib, and Xeloda, also known as capecitabine.
 
The patients getting Kadcyla lived a median of 30.9 months, compared with 25.1 months for those getting the two pills. The median time before the disease worsened was 9.6 months for those getting Kadcyla, compared with 6.4 months for those getting the other drugs.
 
While having greater efficacy, Kadcyla also had fewer side effects. About 43 percent of patients on Kadcyla had serious side effects compared with 59 percent of those getting the two pills.
 
Still, the label of Kadcyla has a warning saying the drug can cause liver toxicity, heart toxicity and death. It also can cause serious birth defects or fetal death, so women of childbearing age taking the drug are urged to use contraception.
 
Herceptin, also known as trastuzumab, binds to a protein on the surface of breast cancer cells called HER2. Since Kadcyla, known generically as ado-trastuzumab emtansine, incorporates Herceptin, it, too, is approved only for the roughly 20 percent of breast cancer cases with an overabundance of HER2. Kadcyla's approval is for use after a patient has already failed to respond to Herceptin and a taxane. But Roche, the Swiss company that owns Genentech, is already testing it for use as an initial treatment for metastatic cancer. It is also testing it in combination with Perjeta, another of its drugs for HER2-positive breast cancer, which was approved in June.
 
Roche executives say they hope that Kadcyla, along with Perjeta, will make Herceptin somewhat obsolete by the time it could face competition from cheaper biosimilars, which are similar to generics. Roche says the United States patent on Herceptin expires in 2019.
 
Herceptin had global sales of 5.9 billion Swiss francs ($6.3 billion at current exchange rates) in 2012. It was the world's best-selling drug used only for cancer in 2012.
 
 
 
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