PMID- 30420181
OWN - NLM
STAT- MEDLINE
DCOM- 20200326
LR  - 20200326
IS  - 1938-0666 (Electronic)
IS  - 1526-8209 (Linking)
VI  - 19
IP  - 1
DP  - 2019 Feb
TI  - Phase 1b Study of Trebananib Plus Paclitaxel and Trastuzumab in Patients With 
      HER2-Positive Locally Recurrent or Metastatic Breast Cancer.
PG  - 47-57
LID - S1526-8209(18)30451-8 [pii]
LID - 10.1016/j.clbc.2018.09.012 [doi]
AB  - INTRODUCTION: Trebananib, a peptide-Fc fusion protein, blocks angiogenesis by 
      inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. 
      Trebananib plus trastuzumab and paclitaxel was evaluated in human epidermal 
      growth factor receptor 2-positive breast cancer in an open-label phase 1b 
      clinical study. PATIENTS AND METHODS: Women with human epidermal growth factor 
      receptor 2-positive breast cancer received weekly paclitaxel (80 mg/m(2)), 
      trastuzumab (8 mg/m(2) then 6 mg/kg every 3 weeks), and intravenous trebananib 
      (10 mg/kg or 30 mg/kg weekly) beginning week 2. The primary end point was the 
      incidence of dose-limiting toxicities. Secondary end points included incidence of 
      adverse events (AEs), pharmacokinetics, and tumor response (objective response 
      and duration of response). RESULTS: Forty women were enrolled; 2 experienced 
      dose-limiting toxicities (grade 3 ocular transient ischemic attack [10 mg/kg 
      cohort] and grade 3 elevation in gamma-glutamyl transferase [30 mg/kg cohort]). The 
      most common treatment-emergent AEs were peripheral edema (n = 28), diarrhea (n = 
      27), alopecia (n = 26), fatigue (n = 24), and nausea (n = 24). Maximum observed 
      concentration and area under the concentration-time curve increased 
      proportionally with the trebananib dose. Objective response was confirmed in 31 
      patients. In the 10 mg/kg cohort, 16 patients (80%) experienced partial response, 
      and none experienced complete response. In the 30 mg/kg cohort, 12 patients (71%) 
      experienced partial response and 3 (18%) experienced complete response. Median 
      (95% confidence interval) duration of response in the 10 and 30 mg/kg cohorts was 
      12.6 (4.3-20.2) and 16.6 (8.2-not estimable) months, respectively. CONCLUSION: 
      This phase 1b study showed that trebananib was tolerated with manageable AEs at a 
      dose up to 30 mg/kg weekly. Trebananib demonstrated anticancer activity, as 
      indicated by objective response and duration of response.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Kaufman, Peter A
AU  - Kaufman PA
AD  - Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, NH. 
      Electronic address: Peter.a.kaufman@dartmouth.edu.
FAU - Wildiers, Hans
AU  - Wildiers H
AD  - KU Leuven and Department of General Medical Oncology, University Hospitals 
      Leuven, Leuven, Belgium.
FAU - Freyer, Gilles
AU  - Freyer G
AD  - Medical Oncology, HCL Cancer Institute and Lyon 1 University, Lyon, France.
FAU - Kemeny, Margaret
AU  - Kemeny M
AD  - Queens Cancer Center, Queens, NY.
FAU - Goncalves, Anthony
AU  - Goncalves A
AD  - Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.
FAU - Jerusalem, Guy
AU  - Jerusalem G
AD  - Department of Medical Oncology, CHU Sart Tilman Liege and Liege University, 
      Liege, Belgium.
FAU - Stopeck, Alison
AU  - Stopeck A
AD  - Division of Hematology/Oncology, Stony Brook Cancer Center, Stony Brook, NY.
FAU - Vrindavanam, Nandagopal
AU  - Vrindavanam N
AD  - Department of Clinical Research, Signal Point Clinical Research Center, LLC, 
      Middletown, OH.
FAU - Dalenc, Florence
AU  - Dalenc F
AD  - Department of Medical Oncology, Institut Claudius Regaud, IUCT-Oncopole, 
      Toulouse, France.
FAU - Nanayakkara, Nuwan
AU  - Nanayakkara N
AD  - Quintiles, San Diego, CA.
FAU - Wu, Benjamin
AU  - Wu B
AD  - Department of Medical Sciences, Amgen Inc, Thousand Oaks, CA.
FAU - Pickett, Cheryl A
AU  - Pickett CA
AD  - Department of Clinical Development, Amgen Inc, Thousand Oaks, CA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20181009
PL  - United States
TA  - Clin Breast Cancer
JT  - Clinical breast cancer
JID - 100898731
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
RN  - P88XT4IS4D (Paclitaxel)
RN  - X8Y5U6NC7E (trebananib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/metabolism/pathology
MH  - Cohort Studies
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Recurrence, Local/*drug therapy/metabolism/pathology
MH  - Paclitaxel/administration & dosage
MH  - Prognosis
MH  - Receptor, ErbB-2/*metabolism
MH  - Recombinant Fusion Proteins/administration & dosage
MH  - Trastuzumab/administration & dosage
OTO - NOTNLM
OT  - AMG 386
OT  - Angiogenesis
OT  - Angiopoietin
OT  - HER2 positive
EDAT- 2018/11/14 06:00
MHDA- 2020/03/27 06:00
CRDT- 2018/11/14 06:00
PHST- 2018/06/27 00:00 [received]
PHST- 2018/09/21 00:00 [revised]
PHST- 2018/09/29 00:00 [accepted]
PHST- 2018/11/14 06:00 [pubmed]
PHST- 2020/03/27 06:00 [medline]
PHST- 2018/11/14 06:00 [entrez]
AID - S1526-8209(18)30451-8 [pii]
AID - 10.1016/j.clbc.2018.09.012 [doi]
PST - ppublish
SO  - Clin Breast Cancer. 2019 Feb;19(1):47-57. doi: 10.1016/j.clbc.2018.09.012. Epub 
      2018 Oct 9.