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Revision as of 13:50, 10 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,054 edits Saving copy of the {{drugbox}} taken from revid 460518768 of page Trastuzumab_emtansine for the Chem/Drugbox validation project (updated: 'UNII', 'KEGG', 'CAS_number').		Latest revision as of 14:16, 27 July 2024 edit Rofraja (talk | contribs)Extended confirmed users, Pending changes reviewers24,019 edits Fix bare URLs references, add title
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			{{Short description|Pharmaceutical drug}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
			{{distinguish|Trastuzumab}}
			{{Use dmy dates|date=February 2022}}
	{{Drugbox		{{Drugbox
	| Verifiedfields = changed		| Verifiedfields = changed
			| Watchedfields = changed
	| verifiedrevid = 421136173
			| verifiedrevid = 470612501
	| IUPAC_name =
			| drug_name =
	| image = Emtansine mab structure coloured.svg
			| INN =
			| image = Trastuzumab emtansine.svg
			| width = 300
			| alt =
			| caption =
	<!--Monoclonal antibody data-->		<!-- Monoclonal antibody data -->
	| type = mab		| type = mab
	| mab_type = mab		| mab_type = mab
	| source = zu/o		| source = zu/o
	<!--Clinical data-->		<!-- Clinical data -->
	| tradename =		| pronounce =
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->		| tradename = Kadcyla
			| Drugs.com = {{drugs.com|monograph|ado-trastuzumab-emtansine}}
	| pregnancy_US = <!-- A / B / C / D / X -->
			| MedlinePlus = a613031
	| pregnancy_category =
			| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) -->
	| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
			| licence_EU = yes
	| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
			| DailyMedID = Trastuzumab_emtansine
	| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
			| licence_US = Kadcyla
	| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
			| pregnancy_AU = D
	| legal_status = Investigational
			| pregnancy_AU_comment = <ref name="Drugs.com Pregnancy">{{drugs.com|pregnancy|ado-trastuzumab-emtansine}}</ref>
	| routes_of_administration =
			| pregnancy_category =
			| routes_of_administration = ]
			| class = Antineoplastic agent
			| ATCvet =
			| ATC_prefix = L01
			| ATC_suffix = FD03
			| ATC_supplemental =
	<!--Pharmacokinetic data-->		<!-- Legal status -->
	| bioavailability =		| legal_AU = S4
			| legal_AU_comment = <ref name="Kadcyla PI">{{Cite web | url=https://www.guildlink.com.au/gc/ws/ro/pi.cfm?product=ropkadcy20714 | title=Kadcyla® (trastuzumab emtansine) | website=www.guildlink.com.au | access-date=2024-07-27}}</ref>
	| protein_bound =
			| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
	| metabolism =
			| legal_BR_comment =
	| elimination_half-life =
			| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
	| excretion =
			| legal_CA_comment =
			| legal_DE = <!-- Anlage I, II, III or Unscheduled-->
			| legal_DE_comment =
			| legal_NZ = <!-- Class A, B, C -->
			| legal_NZ_comment =
			| legal_UK = POM
			| legal_UK_comment = <ref name="Kadcyla SmPC" />
			| legal_US = Rx-only
			| legal_US_comment = <ref name="Kadcyla FDA label" />
			| legal_EU = Rx-only
			| legal_EU_comment = <ref name="Kadcyla EPAR" />
			| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
			| legal_UN_comment =
			| legal_status = <!--For countries not listed above-->
	<!--Identifiers-->		<!-- Pharmacokinetic data -->
			| bioavailability = N/A
	| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
			| protein_bound = 93% (in vitro)
	| ChemSpiderID = NA
			| metabolism = ] (]/]-mediated)
	| CAS_number_Ref = {{cascite|correct|??}}
			| metabolites =
	| CAS_number = <!-- blanked - oldvalue: 1018448-65-1 -->
			| onset =
	| ATC_prefix = None
			| elimination_half-life = 4 days
	| ATC_suffix =
			| duration_of_action =
	| ATC_supplemental =
	| PubChem =		| excretion =
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank =
	| UNII_Ref = {{fdacite|changed|FDA}}
	| UNII = <!-- blanked - oldvalue: SE2KH7T06F -->
	| KEGG_Ref = {{keggcite|changed|kegg}}
	| KEGG = <!-- blanked - oldvalue: D09980 -->
	| synonyms =
	<!--Chemical data-->		<!-- Identifiers -->
			| CAS_number_Ref = {{cascite|changed|??}}
	| chemical_formula = C<sub>6448</sub>H<sub>9948</sub>N<sub>1720</sub>O<sub>2012</sub>S<sub>44</sub>·(C<sub>47</sub>H<sub>62</sub>ClN<sub>4</sub>O<sub>13</sub>S)<sub>n</sub>
			| CAS_number = 1018448-65-1
			| CAS_supplemental =
			| PubChem =
			| PubChemSubstance = 347910224
			| IUPHAR_ligand =
			| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
			| DrugBank = DB05773
			| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
			| ChemSpiderID = none
			| UNII_Ref = {{fdacite|changed|FDA}}
			| UNII = SE2KH7T06F
			| KEGG_Ref = {{keggcite|changed|kegg}}
			| KEGG = D09980
			| ChEBI =
			| ChEMBL = 1743082
			| NIAID_ChemDB =
			| PDB_ligand =
			| synonyms = ado-trastuzumab emtansine, trastuzumab-DM1, T-DM1
			<!-- Chemical and physical data -->
	| molecular_weight = 148.5 ]
	| smiles =		| IUPAC_name =
			| chemical_formula_ref = {{cn|date=September 2021}}
			| chemical_formula = C<sub>6448</sub>H<sub>9948</sub>N<sub>1720</sub>O<sub>2012</sub>S<sub>44</sub>·(C<sub>47</sub>H<sub>62</sub>ClN<sub>4</sub>O<sub>13</sub>S)<sub>n</sub>
			| C= | H= | Ag= | Al= | As= | Au= | B= | Bi= | Br= | Ca= | Cl= | Co= | F= | Fe= | Gd= | I=
			| K= | Li= | Mg= | Mn= | N= | Na= | O= | P= | Pt= | S= | Sb= | Se= | Sr= | Tc= | Zn= | charge=
			| molecular_weight = 148.5
			| molecular_weight_comment = kg/mol{{cn|date=September 2021}}
			| SMILES =
			| StdInChI =
			| StdInChI_comment =
			| StdInChIKey =
			| density =
			| density_notes =
			| melting_point =
			| melting_high =
			| melting_notes =
			| boiling_point =
			| boiling_notes =
			| solubility =
			| sol_units =
			| specific_rotation =
	}}		}}
			'''Trastuzumab emtansine''',<ref>{{cite journal |pmid=20521224 |title=Trastuzumab emtansine, an antibody-drug conjugate for the treatment of HER2+ metastatic breast cancer | volume=12 | issue=3 |date=June 2010 |journal=Curr. Opin. Mol. Ther. |pages=350–60 |author=Niculescu-Duvaz I}}</ref><ref>{{cite web |url=http://www.ama-assn.org/resources/doc/usan/trastuzumab-emtansine.pdf |title=Statement On A Nonproprietary Name Adopted By The Usan Council: Trastuzumab Emtansine |author=USAN Council |year=2009 |publisher=] |access-date=22 February 2013 |archive-date=28 September 2012 |archive-url=https://web.archive.org/web/20120928065353/http://www.ama-assn.org/resources/doc/usan/trastuzumab-emtansine.pdf |url-status=dead }}</ref> sold under the brand name '''Kadcyla''', is an ] consisting of the humanized ] ] (Herceptin) covalently linked to the ] agent ].<ref name=LoRusso2011>{{cite journal |vauthors=LoRusso PM, Weiss D, Guardino E, Girish S, Sliwkowski MX |title=Trastuzumab emtansine: a unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer |journal=Clin. Cancer Res. |volume=17 |issue=20 |pages=6437–47 |date=October 2011 |pmid=22003071 |doi=10.1158/1078-0432.CCR-11-0762|doi-access=free }}</ref><ref name=Poon2010>{{cite conference |url=http://www.toxicology.org/isot/rc/NorCal/docs/2010Spring/2010_6SafetyAntibodyDrugConjugates.pdf |title=Safety Assessment of Antibody Drug Conjugates |last=Poon |first=Kirsten Achilles |date=6 May 2010 |conference=''Drug Development: From Small Molecules to Biologics''. NorCal Society of Toxicology 2010 Spring Meeting |access-date=23 February 2013 |archive-date=13 April 2014 |archive-url=https://web.archive.org/web/20140413154738/http://www.toxicology.org/isot/rc/NorCal/docs/2010Spring/2010_6SafetyAntibodyDrugConjugates.pdf |url-status=dead }}</ref><ref name="NCI">{{cite web |url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/ado-trastuzumab-emtansine |title=Trastuzumab emtansine |publisher=] (NCI) |access-date=23 February 2013}}</ref><ref>{{cite press release|url=http://www.news-medical.net/news/20100827/FDA-denies-accelerated-approval-of-Genentechs-trastuzumab-DM1-%28T-DM1%29-BLA-for-metastatic-breast-cancer.aspx |title=FDA denies accelerated approval of Genentech's trastuzumab-DM1 (T-DM1) BLA for metastatic breast cancer |date=27 August 2010 |publisher=Genentech |access-date=23 February 2013}}</ref> Trastuzumab alone stops growth of cancer cells by binding to the ] receptor, whereas trastuzumab emtansine undergoes receptor-mediated internalization into cells, is catabolized in lysosomes where DM1-containing catabolites are released and subsequently bind ] to cause mitotic arrest and cell death.<ref name="NEJM-Teicher">{{cite journal |vauthors=Teicher BA, Doroshow JH |title=The promise of antibody-drug conjugates |journal=N. Engl. J. Med. |volume=367 |issue=19 |pages=1847–8 |date=November 2012 |pmid=23134386 |doi=10.1056/NEJMe1211736}}</ref> Trastuzumab binding to HER2 prevents homodimerization or heterodimerization (HER2/HER3) of the receptor, ultimately inhibiting the activation of ] and ] cellular signalling pathways. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the cytotoxic agent DM1 specifically to tumor cells.<ref name="NEJM-Verma"/> The conjugate is abbreviated '''T-DM1'''.
			In the EMILIA clinical trial<ref name=NCT00829166 /> of women with advanced ] ] who were already resistant to trastuzumab alone, it improved median ] by 5.8 months (30.9 months vs. 25.1 months) compared to the combination of ] and ].<ref name="NEJM-Verma"/> Based on that trial, the U.S. ] (FDA) approved marketing on 22 February 2013.<ref>{{cite press release |url=http://www.roche.com/med-cor-2012-08-27 |title=New data from Phase III EMILIA study showed Roche's trastuzumab emtansine (T-DM1) significantly improved survival of people with HER2-positive metastatic breast cancer |publisher=] |date=27 August 2012 |access-date=23 February 2013 |archive-date=4 November 2021 |archive-url=https://web.archive.org/web/20211104232732/https://www.roche.com/media/releases/med-cor-2012-08-27.htm |url-status=dead }}</ref><ref name="NYT">{{cite news |url=https://www.nytimes.com/2013/02/23/business/fda-approves-breast-cancer-drug.html|title=F.D.A. Approves a New Drug for Advanced Breast Cancer |last=Pollack |first=Andrew |date=22 February 2013 |access-date=22 February 2013 |work=] | name-list-style=vanc}}</ref><ref name="FDA PR">{{cite press release|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm340704.htm |title=FDA approves new treatment for late-stage breast cancer |publisher=U.S. ] (FDA) |date=22 February 2013|access-date=22 February 2013 | archive-url=https://web.archive.org/web/20170112023904/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm340704.htm | archive-date=12 January 2017 | url-status=dead }} {{PD-notice}}</ref>
			Trastuzumab emtansine was developed by ], and is manufactured by ].<ref>{{cite news |last=Franklin|first=Joshua|date=24 July 2014|title=Lonza profit boosted by drug production outsourcing|url=https://www.reuters.com/article/lonza-group-results-idUSL6N0PZ11U20140724|newspaper=]|access-date=28 July 2014 | name-list-style=vanc}}</ref>
			==Medical uses==
			In the United States, trastuzumab emtansine was approved specifically for treatment of HER2-positive ] (mBC) in patients who have been treated previously with trastuzumab and a ] (] or ]), and who have already been treated for mBC or developed tumor ] within six months of ].<ref name="FDA Approval" /><ref name="Kadcyla FDA label">{{cite web | title=Kadcyla- ado-trastuzumab emtansine injection, powder, lyophilized, for solution | website=] | date=16 May 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=23f3c1f4-0fc8-4804-a9e3-04cf25dd302e | access-date=4 December 2019}}</ref>
			Approval was based on the EMILIA study,<ref name=NCT00829166>{{ClinicalTrialsGov|NCT00829166|A Study of Trastuzumab Emtansine Versus Capecitabine + Lapatinib in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer (EMILIA)}}</ref> a phase III ] that compared trastuzumab emtansine versus ] (Xeloda) plus ] (Tykerb) in 991 people with unresectable, locally advanced or metastatic HER2-positive breast cancer who had previously been treated with trastuzumab and taxane ].<ref name=NCT00829166 /> This trial showed improved ] in patients treated with trastuzumab emtansine (median 9.6 vs. 6.4 months), along with improved ] (median 30.9 vs. 25.1 months) and safety.<ref name="NEJM-Verma">{{cite journal |vauthors=Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K | display-authors=3 |title= Trastuzumab emtansine for HER2-positive advanced breast cancer |journal=N. Engl. J. Med. |volume=367|issue=19 |pages=1783–91 |date=November 2012 |pmid=23020162 |doi= 10.1056/NEJMoa1209124 |pmc=5125250 }}</ref>
			==Adverse effects==
			During clinical trials, the most common ]s of trastuzumab emtansine were fatigue, nausea, musculoskeletal pain, ] (low ] counts), headache, ], and constipation.<ref name="Kadcyla FDA label"/>
			Severe adverse events identified during the EMILIA trial included ] (liver damage), including rare cases of ], ], and ]; heart damage (dysfunction of the ]); ], including ]; thrombocytopenia; and ].<ref name="Kadcyla FDA label"/> Overall, trastuzumab emtansine was better tolerated than the control treatment, a combination of ] (Tykerb) and ] (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.<ref name="Kadcyla FDA label"/> ], low platelet counts, and peripheral neuropathy were more common among patients who received trastuzumab emtansine, whereas heart damage and gastrointestinal effects, such as vomiting, diarrhea, and ], were more common with lapatinib/capecitabine.<ref name="Kadcyla FDA label"/>
			In the United States, trastuzumab emtansine carries ]s for liver toxicity, heart damage (reduction in left ventricular ]), and ] if given to pregnant women.<ref name="Kadcyla FDA label"/><ref name="FDA PR" />
			==Chemical properties==
			] skeleton is shown in black at left. The ] group that makes ] is shown in red. The linker group that makes ] is shown in blue at right, bound to the ] group (HN–) of a ] residue in the trastuzumab molecule (–mab).]]
			Trastuzumab emtansine is an ] (ADC), a combination between a ] and a ]. Each molecule of trastuzumab emtansine consists of a single trastuzumab molecule with several molecules of DM1, a ] ], attached.<ref name="Girish">{{cite journal |vauthors=Girish S, Gupta M, Wang B, etal |title=Clinical pharmacology of trastuzumab emtansine (T-DM1): an antibody-drug conjugate in development for the treatment of HER2-positive cancer |journal=Cancer Chemother. Pharmacol. |volume=69 |issue=5 |pages=1229–40 |date=May 2012 |pmid=22271209 |pmc=3337408 |doi=10.1007/s00280-011-1817-3}}</ref> SMCC, or succinimidyl ''trans''-4-(maleimidylmethyl)cyclohexane-1-carboxylate, is a ''heterobifunctional crosslinker'', a type of ] that contains two reactive ]s, a ] ] and a ]. The succinimide group of SMCC reacts with the free ] group of a ] residue in the trastuzumab molecule{{Failed verification|date=September 2015|Per WHO (see image source), there is no (additional) succinimide in the linker.}} and the maleimide moiety of SMCC links to the free sulfhydryl group of DM1, forming a ] between the antibody and the DM1. Each trastuzumab molecule may be linked to zero to eight DM1 molecules (3.5 on average).<ref name="Girish"/><ref name="LewisPhillips">{{cite journal |vauthors=Lewis Phillips GD, Li G, Dugger DL, etal |title=Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate |journal=Cancer Res. |volume=68 |issue=22 |pages=9280–90 |date=November 2008 |pmid=19010901 |doi=10.1158/0008-5472.CAN-08-1776|doi-access=free }}</ref> DM1 binds at plus ends of cellular ] and thereby inhibits ] in the target tumor cells.<ref>{{cite journal|vauthors=Lopus M|title=Antibody-DM1 conjugates as cancer therapeutics|journal=Cancer Letters|date=August 2011|volume=307|issue=2|pages=113–118|doi=10.1016/j.canlet.2011.03.017|pmid=21481526|pmc=3105156 }}</ref>
			==History==
			In 2013, trastuzumab emtansine was approved in the United States for the treatment of adults with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.<ref name="FDA PR" /><ref name="FDA Approval">{{cite web | title=Drug Approval Package: ado-trastuzumab emtansine | website=U.S. ] (FDA) | date=22 February 2013 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/125427Orig1s000TOC.cfm | archive-url=https://web.archive.org/web/20191204061612/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/125427Orig1s000TOC.cfm | archive-date=4 December 2019 | url-status=live | access-date=3 December 2019}} {{PD-notice}}</ref>
			Referred to as T-DM1 during clinical research, trastuzumab emtansine was reviewed under the FDA's ] program.<ref name="FDA PR" />
			The safety and effectiveness of trastuzumab emtansine were evaluated in a clinical study of 991 patients randomly assigned to receive trastuzumab emtansine or lapatinib plus capecitabine, another chemotherapy drug.<ref name="FDA PR" /> Patients received treatment until either the cancer progressed or the side effects became intolerable.<ref name="FDA PR" /> The study was designed to measure progression-free survival, the length of time patients lived without the cancer progressing, and overall survival, the length of time patients lived before death.<ref name="FDA PR" />
			Results showed that patients treated with trastuzumab emtansine had a median progression-free survival of 9.6 months compared to 6.4 months in patients treated with lapatinib plus capecitabine.<ref name="FDA PR" /> The median overall survival was 30.9 months in the trastuzumab emtansine group and 25.1 months in the lapatinib plus capecitabine group.<ref name="FDA PR" />
			The U.S. ] (FDA) approved trastuzumab emtansine in February 2013, and granted the application for Kadcyla to Genentech.<ref name="FDA PR" /> The FDA granted the application for trastuzumab emtansine ] and ] designations.<ref name="FDA PR 2" />
			In 2013, trastuzumab emtansine was approved in the UK,<ref name="Kadcyla SmPC">{{cite web | title=Kadcyla 100 mg Powder for Concentrate for Solution for Infusion - Summary of Product Characteristics (SmPC) | website=electronic medicines compendium (emc) | date=19 November 2019 | url=https://www.medicines.org.uk/emc/product/5252/smpc | archive-url=https://web.archive.org/web/20191204070314/https://www.medicines.org.uk/emc/product/5252/smpc | archive-date=4 December 2019 | url-status=live | access-date=3 December 2019}}</ref> and the EU.<ref name="Kadcyla EPAR">{{cite web | title=Kadcyla EPAR | website=] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/kadcyla }}</ref>
			In 2019, trastuzumab emtansine was approved in the United States for the adjuvant treatment of patients with HER2-positive early breast cancer (EBC) who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment.<ref name="FDA PR 2">{{cite press release | title=FDA approves ado-trastuzumab emtansine for early breast cancer | website=U.S. ] (FDA) | date=6 May 2019 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ado-trastuzumab-emtansine-early-breast-cancer | archive-url=https://web.archive.org/web/20190928075144/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ado-trastuzumab-emtansine-early-breast-cancer | archive-date=28 September 2019 | url-status=live | access-date=3 December 2019}} {{PD-notice}}</ref>
			Approval was based on KATHERINE (NCT01772472<ref>{{ClinicalTrialsGov|NCT01772472|A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE)}}</ref>), a randomized, multicenter, open-label trial of 1486 patients with HER2-positive EBC.<ref name="FDA PR 2" /> Breast tumor samples were required to demonstrate HER2 overexpression defined as 3+ IHC or ISH amplification ratio ≥ 2.0 determined at a central laboratory using Ventana's PATHWAY anti-HER2-/neu (4B5) Rabbit Monoclonal Primary Antibody or INFORM HER2 Dual ISH DNA Probe Cocktail assays.<ref name="FDA PR 2" /> Patients were required to have had neoadjuvant taxane and trastuzumab-based therapy with residual invasive tumor in the breast and/or axillary lymph nodes.<ref name="FDA PR 2" /> Patients received radiotherapy and/or hormonal therapy concurrent with study treatment per local guidelines.<ref name="FDA PR 2" /> Patients were randomized (1:1) to receive trastuzumab emtansine 3.6&nbsp;mg/kg intravenously or trastuzumab 6&nbsp;mg/kg intravenously on day 1 of a 21-day cycle for 14 cycles.<ref name="FDA PR 2" />
			The trial's primary endpoint was invasive disease-free survival (IDFS), defined as the time from the date of randomization to first occurrence of ipsilateral invasive breast tumor recurrence, ipsilateral local or regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause.<ref name="FDA PR 2" /> After a median follow-up of 40 months, the trial demonstrated a statistically significant improvement in IDFS in patients who received trastuzumab emtansine compared with those who received trastuzumab (HR 0.50; 95% CI: 0.39, 0.64; p<0.0001).<ref name="FDA PR 2" /> Overall survival data were not mature at the time of the IDFS analysis.<ref name="FDA PR 2" />
			== Society and culture ==
			=== Economics ===
			In the UK, trastuzumab emtansine was not recommended for use by the ] by advisory body ], reportedly because an acceptable pricing agreement could not be reached with ].<ref>{{cite news|last1=Triggle|first1=Nick|title=NHS says no to new breast cancer drug Kadcyla|url=https://www.bbc.co.uk/news/health-28688311|publisher=]|date=8 August 2014|access-date=8 August 2014 | name-list-style=vanc}}</ref> Originally it cost £5,900 a month.<ref name=Gn2015></ref> and NICE estimated it cost £166,000 per ]<ref name=N-8-2014>{{Cite web |url=https://www.nice.org.uk/news/article/pressure-grows-on-roche-to-lower-breast-cancer-drug-price |title=Pressure grows on Roche to lower breast cancer drug price. Aug 2014 |access-date=13 November 2015 |archive-date=9 June 2021 |archive-url=https://web.archive.org/web/20210609155140/http://www.nice.org.uk/News/Article/pressure-grows-on-roche-to-lower-breast-cancer-drug-price |url-status=dead }}</ref> (well over the usual maximum). It has been funded by the English NHS ] but in January 2015 it was proposed to remove it from the approved list.<ref>{{cite news|title=David Cameron's flagship Cancer Drugs Fund 'is a waste of NHS cash'|url=https://www.theguardian.com/politics/2015/jan/10/cancer-drugs-fund-waste-of-nhs-cash-david-cameron|access-date=11 January 2015|publisher=Guardian|date=10 January 2015}}</ref> After a secret discount was agreed by Roche the Cancer Drugs Fund will continue to fund it.<ref name=Gn2015/>
			In June 2017, the NHS Confederation and NHS Chief Executive Simon Stevens announced that the NHS would be offering trastuzumab emtansine to a limited number of women after striking a deal with Roche on the price.<ref>{{Cite news|url=https://nursingnotes.co.uk/nhs-u-turn-sees-breast-cancer-drug-kadcyla-approved-for-use/|title=NHS U-turn sees breast cancer drug Kadcyla approved for use|date=16 June 2017|work=NursingNotes|access-date=16 June 2017|language=en-GB|archive-date=3 June 2019|archive-url=https://web.archive.org/web/20190603101944/https://nursingnotes.co.uk/nhs-u-turn-sees-breast-cancer-drug-kadcyla-approved-for-use/|url-status=dead}}</ref>
			=== Names ===
			In 2013, trastuzumab emtansine was approved in the United States with the generic name "ado-trastuzumab emtansine",<ref name="FDA PR" /><ref name="FDA Approval" /> rather than the original ] (USAN) issued in 2009, "trastuzumab emtansine".<ref name="FDA Approval" /> Trastuzumab is the anti-HER2 antibody; emtansine refers to the linker-drug (SMCC-DM1). The "ado-" prefix was added at the request of the FDA to help prevent ].<ref>{{cite web | title=Drug Safety Communication: FDA warns about potential medication errors resulting from confusion regarding nonproprietary name for breast cancer drug Kadcyla (ado-trastuzumab emtansine) | website=U.S. ] (FDA) | date=16 January 2016 | url=https://www.fda.gov/drugs/drug-safety-and-availability/drug-safety-communication-fda-warns-about-potential-medication-errors-resulting-confusion-regarding | archive-url=https://web.archive.org/web/20191204063358/https://www.fda.gov/drugs/drug-safety-and-availability/drug-safety-communication-fda-warns-about-potential-medication-errors-resulting-confusion-regarding | archive-date=4 December 2019 | url-status=live | access-date=3 December 2019}} {{PD-notice}}</ref><ref name="FDA Approval" /><ref>{{cite tech report |url=http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/125427Orig1s000Sumr.pdf |title=Summary Review for Regulatory Action |vauthors=Kim TE, Pazdur R |publisher=U.S. Food and Drug Administration |page=8 |year=2013 |access-date=22 February 2013}} {{PD-notice}}</ref> During ] and clinical trials, the drug was also known as trastuzumab-DM1 or trastuzumab-MCC-DM1 (after the codename for ]), both abbreviated T-DM1, and by the codename PRO132365.<ref name="NCI"/>
			== Research ==
			===Clinical trials===
			Since 2013 there have been some more clinical trials:
			* First line treatment for metastatic breast cancer: the MARIANNE study<ref>{{ClinicalTrialsGov|NCT01120184|A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab (Herceptin) Plus a Taxane in Patients With Metastatic Breast Cancer (MARIANNE)}}. Retrieved 23 February 2013.</ref> compares taxane (] or ]) plus trastuzumab vs T-DM1 vs T-DM1 plus ] as first-line treatment for people with HER2 positive unresectable locally advanced or metastatic breast cancer; On 19 December 2014, Roche reported the results of the MARIANNE study. Neither Kadcyla-containing treatment significantly improved progression-free survival compared to Herceptin and chemotherapy.<ref>{{citation |url=http://www.roche.com/med-cor-2014-12-19-e.pdf |title=Roche provides update on Phase III MARIANNE study in people with previously untreated advanced HER2-positive breast cancer |year=2014 |access-date=16 January 2015 |archive-date=24 September 2015 |archive-url=https://web.archive.org/web/20150924092008/http://www.roche.com/med-cor-2014-12-19-e.pdf |url-status=dead }}</ref>
			* a phase III trial for HER2+ ] compares T-DM1 to physician's choice of taxane (docetaxel or paclitaxel).<ref>{{ClinicalTrialsGov|NCT01641939|A Study of Trastuzumab Emtansine Versus Taxane in Patients With Advanced Gastric Cancer}}. Retrieved 23 February 2013.</ref> On 22 October 2015, Roche and co-developer ] disclosed that trastuzumab emtansine had failed to meet its primary endpoint in the Phase II/III GATSBY trial investigating the second line treatment of ]-positive advanced gastric cancer.<ref>{{cite web| url= http://www.genengnews.com/gen-news-highlights/roche-s-kadcyla-fails-phase-ii-iii-trial-for-gastric-cancer/81251888/| title= Roche's Kadcyla Fails Phase II/III Trial for Gastric Cancer| date= 22 October 2015| work= Genetic Engineering & Biotechnology News| access-date= 26 May 2017| archive-date= 24 October 2015| archive-url= https://web.archive.org/web/20151024211818/http://www.genengnews.com/gen-news-highlights/roche-s-kadcyla-fails-phase-ii-iii-trial-for-gastric-cancer/81251888| url-status= dead}}</ref>
			* the TH3RESA study is comparing T-DM1 vs treatment of physician's choice for people with HER2 positive metastatic breast cancer previously treated with trastuzumab and lapatinib.<ref>{{ClinicalTrialsGov|NCT01419197|A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Patients With HER2-Positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-Directed Therapy (TH3RESA)}}. Retrieved 23 February 2013.</ref> Interim results for TH3RESA suggest a doubling of ] from three months to six months.<ref name=TIR2013></ref>
			==References==
			{{reflist}}
			==External links==
			* {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/trastuzumab%20emtansine | publisher = U.S. National Library of Medicine| work = Drug Information Portal| title = Trastuzumab emtansine }}
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