PMID- 20108344
OWN - NLM
STAT- MEDLINE
DCOM- 20100426
LR  - 20220330
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 116
IP  - 6
DP  - 2010 Mar 15
TI  - A randomized phase 2 study of etaracizumab, a monoclonal antibody against 
      integrin alpha(v)beta(3), + or - dacarbazine in patients with stage IV metastatic 
      melanoma.
PG  - 1526-34
LID - 10.1002/cncr.24821 [doi]
AB  - BACKGROUND: The alpha (v) beta (3) (alpha(v)beta(3)) integrin is involved in 
      intracellular signaling regulating cell proliferation, migration, and 
      differentiation and is important for tumor-induced angiogenesis. METHODS: This 
      phase 2, randomized, open-label, 2-arm study was designed to capture safety data 
      and evaluate the antitumor efficacy of etaracizumab (Abegrin), an IgG1 humanized 
      monoclonal antibody against the alpha(v)beta(3) integrin, in patients with 
      previously untreated metastatic melanoma. The objective was to evaluate whether 
      etaracizumab + or - dacarbazine had sufficient clinical activity to warrant 
      further study in a phase 3 clinical trial. RESULTS: One hundred twelve patients 
      were randomized to receive etaracizumab alone (N = 57) or etaracizumab + 
      dacarbazine (N = 55). Safety of etaracizumab + or - dacarbazine was acceptable 
      with infusion-related, gastrointestinal, and metabolic reactions being the most 
      common adverse events (AEs). The majority of AEs were grade 1 or 2 in severity in 
      both study arms; most events were not considered serious, except for 
      cardiovascular (myocardial infarction, atrial fibrillation) and thromboembolic 
      events, which occurred in 3 and 5 patients, respectively. None of the patients in 
      the etaracizumab-alone study arm and 12.7% of patients in the etaracizumab + 
      dacarbazine study arm achieved an objective response. The median duration of 
      objective response in the etaracizumab + dacarbazine study arm was 4.2 months. 
      Stable disease rate, time to progression (TTP), and progression-free survival 
      (PFS) appeared to be similar between the 2 treatment arms. Stable disease 
      occurred in 45.6% of patients in the etaracizumab-alone study arm and 40.0% of 
      patients in the etaracizumab + dacarbazine study arm. Median TTP and median PFS 
      were both 1.8 months in the etaracizumab-alone study arm and 2.5 and 2.6 months 
      in the etaracizumab + dacarbazine study arm, respectively. Median overall 
      survival was 12.6 months in the etaracizumab-alone study arm and 9.4 months in 
      the etaracizumab + dacarbazine study arm. CONCLUSIONS: The survival results in 
      both treatment arms of this study were considered unlikely to result in 
      clinically meaningful improvement over dacarbazine alone.
FAU - Hersey, Peter
AU  - Hersey P
AD  - Newcastle Melanoma Unit, Newcastle, Australia.
FAU - Sosman, Jeffrey
AU  - Sosman J
FAU - O'Day, Steven
AU  - O'Day S
FAU - Richards, Jon
AU  - Richards J
FAU - Bedikian, Agop
AU  - Bedikian A
FAU - Gonzalez, Rene
AU  - Gonzalez R
FAU - Sharfman, William
AU  - Sharfman W
FAU - Weber, Robert
AU  - Weber R
FAU - Logan, Theodore
AU  - Logan T
FAU - Buzoianu, Manuela
AU  - Buzoianu M
FAU - Hammershaimb, Luz
AU  - Hammershaimb L
FAU - Kirkwood, John M
AU  - Kirkwood JM
CN  - Etaracizumab Melanoma Study Group
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Integrin alphaVbeta3)
RN  - 41W9MFI160 (etaracizumab)
RN  - 7GR28W0FJI (Dacarbazine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/administration & dosage/adverse effects/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Dacarbazine/administration & dosage/*therapeutic use
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Integrin alphaVbeta3/*immunology
MH  - Male
MH  - Melanoma/*drug therapy/pathology
MH  - Middle Aged
MH  - Skin Neoplasms/*drug therapy/pathology
EDAT- 2010/01/29 06:00
MHDA- 2010/04/27 06:00
CRDT- 2010/01/29 06:00
PHST- 2010/01/29 06:00 [entrez]
PHST- 2010/01/29 06:00 [pubmed]
PHST- 2010/04/27 06:00 [medline]
AID - 10.1002/cncr.24821 [doi]
PST - ppublish
SO  - Cancer. 2010 Mar 15;116(6):1526-34. doi: 10.1002/cncr.24821.