[13] Trastuzumab binding to HER2 prevents homodimerization or heterodimerization (HER2/HER3) of the receptor, ultimately inhibiting the activation of MAPK and PI3K/AKT cellular signalling pathways.

[19] In the United States, trastuzumab emtansine was approved specifically for treatment of HER2-positive metastatic breast cancer (mBC) in patients who have been treated previously with trastuzumab and a taxane (paclitaxel or docetaxel), and who have already been treated for mBC or developed tumor recurrence within six months of adjuvant therapy.

[20][5] Approval was based on the EMILIA study,[15] a phase III clinical trial that compared trastuzumab emtansine versus capecitabine (Xeloda) plus lapatinib (Tykerb) in 991 people with unresectable, locally advanced or metastatic HER2-positive breast cancer who had previously been treated with trastuzumab and taxane chemotherapy.

[14] During clinical trials, the most common adverse effects of trastuzumab emtansine were fatigue, nausea, musculoskeletal pain, thrombocytopenia (low platelet counts), headache, increased liver enzyme levels, and constipation.

[5] Overall, trastuzumab emtansine was better tolerated than the control treatment, a combination of lapatinib (Tykerb) and capecitabine (Xeloda), with 43% of patients in the trastuzumab emtansine group experiencing severe toxic effects, versus 59% of those who received lapatinib/capecitabine; furthermore, fewer patients had to stop treatment due to adverse effects than with lapatinib or capecitabine.

[5] In the United States, trastuzumab emtansine carries black box warnings for liver toxicity, heart damage (reduction in left ventricular ejection fraction), and fetal harm if given to pregnant women.

[21] SMCC, or succinimidyl trans-4-(maleimidylmethyl)cyclohexane-1-carboxylate, is a heterobifunctional crosslinker, a type of chemical reagent that contains two reactive functional groups, a succinimide ester and a maleimide.

[18] The U.S. Food and Drug Administration (FDA) approved trastuzumab emtansine in February 2013, and granted the application for Kadcyla to Genentech.

[24] Patients were required to have had neoadjuvant taxane and trastuzumab-based therapy with residual invasive tumor in the breast and/or axillary lymph nodes.

[24] In the UK, trastuzumab emtansine was not recommended for use by the National Health Service by advisory body NICE, reportedly because an acceptable pricing agreement could not be reached with Roche.