Trastuzumab emtansine. An inadequately assessed combination of two cytotoxic drugs.

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Trastuzumab emtansine. An inadequately assessed combination of two cytotoxic drugs.

Prescrire Int. 2014 Dec;23(155):289.

PubMed ID

25629144 [ View in PubMed

]

Abstract

There is no consensus on second-line treatment for women with metastatic or locally advanced breast cancer over-expressing HER-2 protein in whom treatment with a taxane + trastuzumab has failed. Capecitabine is one option. Adding lapatinib does not prolong survival. Trastuzumab emtansine (Kadcyla, Roche) has received EU marketing authorisation for use in this setting. It consists of two covalently bound drugs: trastuzumab, a monoclonal antibody that binds to HER-2 receptors, and DM1, a cytotoxic microtubule inhibitor. DM1 is derived from maytansine, a cytotoxic drug abandoned in the 1980s because it proved to be too toxic after systemic administration. Clinical evaluation of trastuzumab emtansine is based on an unblinded trial versus capecitabine + lapatinib in 991 patients. The use of lapatinib in all patients in the control group is questionable. An interim analysis suggested that overall survival was about 6 months longer with trastuzumab emtansine (30.9 versus 25.1 months). In addition to the adverse effects of trastuzumab (thrombocytopenia, heart failure, etc.), trastuzumab emtansine causes frequent and potentially life-threatening hepatic toxicity, peripheral neuropathy, and urinary tract infections. Trastuzumab emtansine appears to be less toxic to the skin and mucous membranes than the capecitabine + lapatinib combination. DM1 is metabolised by cytochrome P450 isoenzymes CYP3A4 and CYP3A5 and is also a P-glycoprotein substrate, creating a potential risk of multiple pharmacokinetic interactions. Trastuzumab emtansine appears to be teratogenic and embryotoxic. The international nonproprietary name of this drug is easily confused with trastuzumab. In practice, it is best to at least wait for the full results of the only available comparative trial of trastuzumab emtansine before drawing conclusions about its harm-benefit balance and its possible use if it represents a real therapeutic advance.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Trastuzumab emtansine	Cytochrome P450 3A5	Protein	Humans	Unknown	Substrate	Details

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
Integrate drug-drug interactions in your software
Trastuzumab emtansine Methimazole	The metabolism of Trastuzumab emtansine can be decreased when combined with Methimazole.
Trastuzumab emtansine Ritonavir	The metabolism of Trastuzumab emtansine can be decreased when combined with Ritonavir.
Trastuzumab emtansine Ketoconazole	The metabolism of Trastuzumab emtansine can be decreased when combined with Ketoconazole.
Trastuzumab emtansine Nefazodone	The metabolism of Trastuzumab emtansine can be decreased when combined with Nefazodone.
Trastuzumab emtansine Itraconazole	The metabolism of Trastuzumab emtansine can be decreased when combined with Itraconazole.