PMID- 21172893
OWN - NLM
STAT- MEDLINE
DCOM- 20110310
LR  - 20220311
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 29
IP  - 4
DP  - 2011 Feb 1
TI  - Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment 
      of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after 
      prior HER2-directed therapy.
PG  - 398-405
LID - 10.1200/JCO.2010.29.5865 [doi]
AB  - PURPOSE: The antibody-drug conjugate trastuzumab-DM1 (T-DM1) combines the 
      biologic activity of trastuzumab with targeted delivery of a potent 
      antimicrotubule agent, DM1, to human epidermal growth factor receptor 2 
      (HER2)-overexpressing cancer cells. Based on results from a phase I study that 
      showed T-DM1 was well tolerated at the maximum-tolerated dose of 3.6 mg/kg every 
      3 weeks, with evidence of efficacy, in patients with HER2-positive metastatic 
      breast cancer (MBC) who were previously treated with trastuzumab, we conducted a 
      phase II study to further define the safety and efficacy of T-DM1 in this patient 
      population. PATIENTS AND METHODS: This report describes a single-arm phase II 
      study (TDM4258g) that assessed efficacy and safety of intravenous T-DM1 (3.6 
      mg/kg every 3 weeks) in patients with HER2-positive MBC who had tumor progression 
      after prior treatment with HER2-directed therapy and who had received prior 
      chemotherapy. RESULTS: With a follow-up of >/= 12 months among 112 treated 
      patients, the objective response rate by independent assessment was 25.9% (95% 
      CI, 18.4% to 34.4%). Median duration of response was not reached as a result of 
      insufficient events (lower limit of 95% CI, 6.2 months), and median 
      progression-free survival time was 4.6 months (95% CI, 3.9 to 8.6 months). The 
      response rates were higher among patients with confirmed HER2-positive tumors 
      (immunohistochemistry 3+ or fluorescent in situ hybridization positive) by 
      retrospective central testing (n = 74). Higher response rates were also observed 
      in patients whose tumors expressed >/= median HER2 levels by quantitative reverse 
      transcriptase polymerase chain reaction for HER2 expression, compared with 
      patients who had less than median HER2 levels. T-DM1 was well tolerated with no 
      dose-limiting cardiotoxicity. Most adverse events (AEs) were grade 1 or 2; the 
      most frequent grade >/= 3 AEs were hypokalemia (8.9%), thrombocytopenia (8.0%), and 
      fatigue (4.5%). CONCLUSION: T-DM1 has robust single-agent activity in patients 
      with heavily pretreated, HER2-positive MBC and is well tolerated at the 
      recommended phase II dose.
FAU - Burris, Howard A 3rd
AU  - Burris HA 3rd
AD  - Sarah Cannon Research Institute, Nashville, TN 37203-1632, USA. 
      howard.burris@scresearch.net
FAU - Rugo, Hope S
AU  - Rugo HS
FAU - Vukelja, Svetislava J
AU  - Vukelja SJ
FAU - Vogel, Charles L
AU  - Vogel CL
FAU - Borson, Rachel A
AU  - Borson RA
FAU - Limentani, Steven
AU  - Limentani S
FAU - Tan-Chiu, Elizabeth
AU  - Tan-Chiu E
FAU - Krop, Ian E
AU  - Krop IE
FAU - Michaelson, Richard A
AU  - Michaelson RA
FAU - Girish, Sandhya
AU  - Girish S
FAU - Amler, Lukas
AU  - Amler L
FAU - Zheng, Maoxia
AU  - Zheng M
FAU - Chu, Yu-Waye
AU  - Chu YW
FAU - Klencke, Barbara
AU  - Klencke B
FAU - O'Shaughnessy, Joyce A
AU  - O'Shaughnessy JA
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20101220
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)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Immunotoxins)
RN  - 0 (RNA, Messenger)
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
CIN - J Clin Oncol. 2011 Feb 1;29(4):351-4. PMID: 21172881
MH  - Ado-Trastuzumab Emtansine
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/adverse effects/pharmacokinetics/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/adverse effects/pharmacokinetics/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/enzymology/genetics/immunology/mortality/pathology
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Immunotoxins/adverse effects/pharmacokinetics/*therapeutic use
MH  - Kaplan-Meier Estimate
MH  - Maytansine/adverse effects/*analogs & derivatives/pharmacokinetics/therapeutic 
      use
MH  - Middle Aged
MH  - RNA, Messenger/analysis
MH  - Receptor, ErbB-2/*antagonists & inhibitors/genetics/metabolism
MH  - Time Factors
MH  - Trastuzumab
MH  - Treatment Outcome
MH  - United States
EDAT- 2010/12/22 06:00
MHDA- 2011/03/11 06:00
CRDT- 2010/12/22 06:00
PHST- 2010/12/22 06:00 [entrez]
PHST- 2010/12/22 06:00 [pubmed]
PHST- 2011/03/11 06:00 [medline]
AID - JCO.2010.29.5865 [pii]
AID - 10.1200/JCO.2010.29.5865 [doi]
PST - ppublish
SO  - J Clin Oncol. 2011 Feb 1;29(4):398-405. doi: 10.1200/JCO.2010.29.5865. Epub 2010 
      Dec 20.