Article (Scientific journals)
Phase 1b Study of Trebananib Plus Paclitaxel and Trastuzumab in Patients With HER2-Positive Locally Recurrent or Metastatic Breast Cancer.
Kaufman, Peter A.; Wildiers, Hans; Freyer, Gilles et al.
2019In Clinical Breast Cancer, 19 (1), p. 47-57
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Keywords :
AMG 386; Angiogenesis; Angiopoietin; HER2 positive
Abstract :
[en] 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.
Disciplines :
Author, co-author :
Kaufman, Peter A.
Wildiers, Hans
Freyer, Gilles
Kemeny, Margaret
Goncalves, Anthony
JERUSALEM, Guy  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service d'oncologie médicale
Stopeck, Alison
Vrindavanam, Nandagopal
Dalenc, Florence
Nanayakkara, Nuwan
Wu, Benjamin
Pickett, Cheryl A.
Language :
Title :
Phase 1b Study of Trebananib Plus Paclitaxel and Trastuzumab in Patients With HER2-Positive Locally Recurrent or Metastatic Breast Cancer.
Publication date :
Journal title :
Clinical Breast Cancer
Publisher :
Cancer Information Group, United States
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2018. Published by Elsevier Inc.
Available on ORBi :
since 29 May 2019


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