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Title: Phase II Study of First-Line Trebananib Plus Sorafenib in Patients with Advanced Hepatocellular Carcinoma.
Austin Authors: Abou-Alfa, Ghassan K;Blanc, Jean-Frederic;Miles, Steven;Ganten, Tom;Trojan, Jörg;Cebon, Jonathan S ;Liem, Andre K;Lipton, Lara;Gupta, Charu;Wu, Benjamin;Bass, Michael;Hollywood, Ellen;Ma, Jennifer;Bradley, Margaret;Litten, Jason;Saltz, Leonard B
Affiliation: Memorial Sloan Kettering Cancer Center, New York, New York, USA
Weill Cornell Medical College, New York, New York, USA
Hôpital Saint-André, Bordeaux, France
Cedars Sinai Hospital, Los Angeles, California, USA
University of Heidelberg, Heidelberg, Germany
Johann Wolfgang Goethe University, Frankfurt, Germany
Olivia Newton-John Cancer Research Institute, Austin Health, Heidelberg, Victoria, Australia
Translational Oncology Research International, Long Beach, California, USA
Western Hospital, Footscray, Victoria, Australia
Amgen Inc., ThoUSAnd Oaks, California, USA
Issue Date: Jul-2017 2017-06-07
Publication information: The oncologist 2017; 22(7): 780-e65
Abstract: 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. 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). 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. 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. There was no improvement in PFS rate at 4 months in either cohort, when compared with sorafenib historical control.
DOI: 10.1634/theoncologist.2017-0058
PubMed URL: 28592620
Type: Journal Article
Appears in Collections:Journal articles

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