Phase II Study of First-Line Trebananib Plus Sorafenib in Patients with Advanced Hepatocellular Carcinoma. Academic Article uri icon

Overview

abstract

  • LESSONS LEARNED: Trebananib leveraging anti-angiogenic mechanism that is distinct from the classic sorafenib anti-vascular endothelial growth factor inhibition did not demonstrate improved progression-free survival at 4 months in patients with advanced hepatocellular carcinoma (HCC).In support of previously reported high Ang-2 levels' association with poor outcome in HCC for patients, trebananib treatment with lower baseline Ang-2 at study entry was associated with improved overall survival to 22 months and may suggest future studies to be performed within the context of low baseline Ang-2. BACKGROUND: Ang-1 and Ang-2 are angiopoietins thought to promote neovascularization via activation of the Tie-2 angiopoietin receptor. Trebananib sequesters Ang-1 and Ang-2, preventing interaction with the Tie-2 receptor. Trebananib plus sorafenib combination has acceptable toxicity. Elevated Ang-2 levels are associated with poor prognosis in hepatocellular carcinoma (HCC). METHODS: Patients with HCC, Eastern Cooperative Oncology Group ≤2, and Childs-Pugh A received IV trebananib at 10 mg/kg or 15 mg/kg weekly plus sorafenib 400 mg orally twice daily. The study was planned for ≥78% progression-free survival (PFS) rate at 4 months relative to 62% for sorafenib historical control (power = 80% α = 0.20). Secondary endpoints included safety, tolerability, overall survival (OS), and multiple biomarkers, including serum Ang-2. RESULTS: Thirty patients were enrolled sequentially in each of the two nonrandomized cohorts. Demographics were comparable between the two arms and the historical controls. PFS rates at 4 months were 57% and 54% on the 10 mg/kg and 15 mg/kg trebananib cohorts, respectively. Median OS was 17 and 11 months, respectively. Grade 3 and above events noted in ≥10% of patients included fatigue, hypertension, diarrhea, liver failure, palmar-plantar erythrodysesthesia syndrome, dyspnea, and hypophosphatemia. One death was due to hepatic failure. Serum Ang-2 dichotomized at the median was associated with improved OS in both cohorts. CONCLUSION: There was no improvement in PFS rate at 4 months in either cohort, when compared with sorafenib historical control.

authors

  • Abou-Alfa, Ghassan
  • Blanc, Jean-Frederic
  • Miles, Steven
  • Ganten, Tom
  • Trojan, Jörg
  • Cebon, Jonathan
  • Liem, Andre K
  • Lipton, Lara
  • Gupta, Charu
  • Wu, Benjamin
  • Bass, Michael
  • Hollywood, Ellen
  • Ma, Jennifer
  • Bradley, Margaret
  • Litten, Jason
  • Saltz, Leonard B.

publication date

  • June 7, 2017

Research

keywords

  • Antineoplastic Combined Chemotherapy Protocols
  • Carcinoma, Hepatocellular
  • Liver Neoplasms

Identity

PubMed Central ID

  • PMC5507650

Scopus Document Identifier

  • 85024122272

Digital Object Identifier (DOI)

  • 10.1634/theoncologist.2017-0058

PubMed ID

  • 28592620

Additional Document Info

volume

  • 22

issue

  • 7