The Committee for Medicinal Products for Human Use ( CHMP ) has adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Kadcyla, 100 mg and 160 mg, powder for concentrate for solution for infusion intended for the treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received Trastuzumab and a taxane, separately or in combination.
The active substance of Kadcyla is Trastuzumab emtansine, an antineoplastic agent which contains the monoclonal antibody Trastuzumab linked to a cytotoxic agent DM1 and acts by the mechanism of actions of both its components; Trastuzumab by binding to HER2 extracellular domain mediates antibody dependent cell -mediated cytotoxicity inhibits shedding of the HER2 ECD and signalling through the PI3-K pathway, whereas targeted delivery of DM1 confers selective cytotoxicity to malignant cells by binding to tubulin and inducing apoptosis.
The benefits with Kadcyla have been shown in a phase III randomised multicentre, international, open label clinical study. In this study, efficacy has been shown in terms of an increased overall survival in patients who received Kadcyla ( median duration of survival 30.9 months ) compared with patients who received control treatment of Lapatinib ( Tykerb ) plus Capecitabine ( Xeloda ) ( 25.1 months ) and increased progression free survival ( 9.6 months versus 6.4 months ).
The most common side effects with Trastuzumab emtansine are haemorrhage ( including epistaxis ), increased transaminases, fatigue, musculoskeletal pain, and headache.
The approved indication is: Kadcyla, as a single agent, is indicated for the treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received Trastuzumab and a taxane, separately or in combination.
Patients should have either: a) received prior therapy for locally advanced or metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy.
Kadcyla should be prescribed by physicians experienced in the treatment of cancer patients. Patients treated with Trastuzumab emtansine should have HER2 positive tumour status, defined as a score of 3+ by immunohistochemistry ( IHC ) or a ratio of greater than or equal to 2.0 by in situ hybridization ( ISH ). ( Xagena )
Source: EMA, 2013