PMID- 25024070
OWN - NLM
STAT- MEDLINE
DCOM- 20141231
LR  - 20191210
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 32
IP  - 25
DP  - 2014 Sep 1
TI  - Trastuzumab emtansine in human epidermal growth factor receptor 2-positive 
      metastatic breast cancer: an integrated safety analysis.
PG  - 2750-7
LID - 10.1200/JCO.2013.54.4999 [doi]
AB  - PURPOSE: The antibody-drug conjugate trastuzumab emtansine (T-DM1) combines the 
      cytotoxic activity of DM1 with the human epidermal growth factor receptor 2 
      (HER2) -targeted, antitumor properties of trastuzumab. T-DM1 has shown activity 
      in phase I and II single-arm studies in patients with pretreated HER2-positive 
      metastatic breast cancer (MBC) and has demonstrated superior efficacy and 
      improved tolerability versus standard MBC treatments in randomized phase II and 
      III studies. This analysis, combining available data from all single-agent T-DM1 
      studies to date, was conducted to better define the T-DM1 safety profile. 
      PATIENTS AND METHODS: Six studies in patients with HER2-positive MBC who received 
      T-DM1 3.6 mg/kg every 3 weeks and follow-up data from patients in an extension 
      study were analyzed. Analyses included adverse events (AEs) by grade; AEs leading 
      to death, drug discontinuation, or dose reduction; and select AEs. RESULTS: Among 
      884 T-DM1-exposed patients, the most commonly reported all-grade AEs were fatigue 
      (46.4%), nausea (43.0%), thrombocytopenia (32.2%), headache (29.4%), and 
      constipation (26.5%). The most common grade 3 to 4 AEs were the laboratory 
      abnormalities of thrombocytopenia (11.9%) and increased AST serum concentration 
      (4.3%). These were manageable and not generally associated with clinical 
      symptoms. There were 12 AE-related deaths. AEs resulted in dose reductions in 
      17.2% of patients and drug discontinuations in 7.0%. CONCLUSION: In this analysis 
      of 884 T-DM1-exposed patients, grade 3 or greater AEs were infrequent and 
      typically asymptomatic and manageable. This favorable safety profile makes T-DM1 
      treatment suitable for exploration in other breast cancer settings.
CI  - (c) 2014 by American Society of Clinical Oncology.
FAU - Dieras, Veronique
AU  - Dieras V
AD  - Veronique Dieras, Institut Curie, Paris, France; Nadia Harbeck, University of 
      Munich, Munich, Germany; G. Thomas Budd, Cleveland Clinic, Lerner College of 
      Medicine, Cleveland, OH; Joel K. Greenson, University of Michigan, Ann Arbor, MI; 
      Ellie A. Guardino, Meghna Samant, Nataliya Chernyukhin, and Melanie C. Smitt, 
      Genentech, South San Francisco, CA; and Ian E. Krop, Dana-Farber Cancer 
      Institute, Boston, MA. veronique.dieras@curie.fr.
FAU - Harbeck, Nadia
AU  - Harbeck N
AD  - Veronique Dieras, Institut Curie, Paris, France; Nadia Harbeck, University of 
      Munich, Munich, Germany; G. Thomas Budd, Cleveland Clinic, Lerner College of 
      Medicine, Cleveland, OH; Joel K. Greenson, University of Michigan, Ann Arbor, MI; 
      Ellie A. Guardino, Meghna Samant, Nataliya Chernyukhin, and Melanie C. Smitt, 
      Genentech, South San Francisco, CA; and Ian E. Krop, Dana-Farber Cancer 
      Institute, Boston, MA.
FAU - Budd, G Thomas
AU  - Budd GT
AD  - Veronique Dieras, Institut Curie, Paris, France; Nadia Harbeck, University of 
      Munich, Munich, Germany; G. Thomas Budd, Cleveland Clinic, Lerner College of 
      Medicine, Cleveland, OH; Joel K. Greenson, University of Michigan, Ann Arbor, MI; 
      Ellie A. Guardino, Meghna Samant, Nataliya Chernyukhin, and Melanie C. Smitt, 
      Genentech, South San Francisco, CA; and Ian E. Krop, Dana-Farber Cancer 
      Institute, Boston, MA.
FAU - Greenson, Joel K
AU  - Greenson JK
AD  - Veronique Dieras, Institut Curie, Paris, France; Nadia Harbeck, University of 
      Munich, Munich, Germany; G. Thomas Budd, Cleveland Clinic, Lerner College of 
      Medicine, Cleveland, OH; Joel K. Greenson, University of Michigan, Ann Arbor, MI; 
      Ellie A. Guardino, Meghna Samant, Nataliya Chernyukhin, and Melanie C. Smitt, 
      Genentech, South San Francisco, CA; and Ian E. Krop, Dana-Farber Cancer 
      Institute, Boston, MA.
FAU - Guardino, Alice E
AU  - Guardino AE
AD  - Veronique Dieras, Institut Curie, Paris, France; Nadia Harbeck, University of 
      Munich, Munich, Germany; G. Thomas Budd, Cleveland Clinic, Lerner College of 
      Medicine, Cleveland, OH; Joel K. Greenson, University of Michigan, Ann Arbor, MI; 
      Ellie A. Guardino, Meghna Samant, Nataliya Chernyukhin, and Melanie C. Smitt, 
      Genentech, South San Francisco, CA; and Ian E. Krop, Dana-Farber Cancer 
      Institute, Boston, MA.
FAU - Samant, Meghna
AU  - Samant M
AD  - Veronique Dieras, Institut Curie, Paris, France; Nadia Harbeck, University of 
      Munich, Munich, Germany; G. Thomas Budd, Cleveland Clinic, Lerner College of 
      Medicine, Cleveland, OH; Joel K. Greenson, University of Michigan, Ann Arbor, MI; 
      Ellie A. Guardino, Meghna Samant, Nataliya Chernyukhin, and Melanie C. Smitt, 
      Genentech, South San Francisco, CA; and Ian E. Krop, Dana-Farber Cancer 
      Institute, Boston, MA.
FAU - Chernyukhin, Nataliya
AU  - Chernyukhin N
AD  - Veronique Dieras, Institut Curie, Paris, France; Nadia Harbeck, University of 
      Munich, Munich, Germany; G. Thomas Budd, Cleveland Clinic, Lerner College of 
      Medicine, Cleveland, OH; Joel K. Greenson, University of Michigan, Ann Arbor, MI; 
      Ellie A. Guardino, Meghna Samant, Nataliya Chernyukhin, and Melanie C. Smitt, 
      Genentech, South San Francisco, CA; and Ian E. Krop, Dana-Farber Cancer 
      Institute, Boston, MA.
FAU - Smitt, Melanie C
AU  - Smitt MC
AD  - Veronique Dieras, Institut Curie, Paris, France; Nadia Harbeck, University of 
      Munich, Munich, Germany; G. Thomas Budd, Cleveland Clinic, Lerner College of 
      Medicine, Cleveland, OH; Joel K. Greenson, University of Michigan, Ann Arbor, MI; 
      Ellie A. Guardino, Meghna Samant, Nataliya Chernyukhin, and Melanie C. Smitt, 
      Genentech, South San Francisco, CA; and Ian E. Krop, Dana-Farber Cancer 
      Institute, Boston, MA.
FAU - Krop, Ian E
AU  - Krop IE
AD  - Veronique Dieras, Institut Curie, Paris, France; Nadia Harbeck, University of 
      Munich, Munich, Germany; G. Thomas Budd, Cleveland Clinic, Lerner College of 
      Medicine, Cleveland, OH; Joel K. Greenson, University of Michigan, Ann Arbor, MI; 
      Ellie A. Guardino, Meghna Samant, Nataliya Chernyukhin, and Melanie C. Smitt, 
      Genentech, South San Francisco, CA; and Ian E. Krop, Dana-Farber Cancer 
      Institute, Boston, MA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140714
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 14083FR882 (Maytansine)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
RN  - SE2KH7T06F (Ado-Trastuzumab Emtansine)
SB  - IM
MH  - Ado-Trastuzumab Emtansine
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/*enzymology/pathology
MH  - Female
MH  - Humans
MH  - Maytansine/adverse effects/*analogs & derivatives/therapeutic use
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Randomized Controlled Trials as Topic
MH  - Receptor, ErbB-2/*metabolism
MH  - Trastuzumab
MH  - Treatment Outcome
EDAT- 2014/07/16 06:00
MHDA- 2015/01/01 06:00
CRDT- 2014/07/16 06:00
PHST- 2014/07/16 06:00 [entrez]
PHST- 2014/07/16 06:00 [pubmed]
PHST- 2015/01/01 06:00 [medline]
AID - JCO.2013.54.4999 [pii]
AID - 10.1200/JCO.2013.54.4999 [doi]
PST - ppublish
SO  - J Clin Oncol. 2014 Sep 1;32(25):2750-7. doi: 10.1200/JCO.2013.54.4999. Epub 2014 
      Jul 14.