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- Title
Phase II Study of First-Line Trebananib Plus Sorafenib in Patients with Advanced Hepatocellular Carcinoma.
- Authors
Abou‐Alfa, Ghassan K.; 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.
- Abstract
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 controll.
- Subjects
ANTINEOPLASTIC agents; CLINICAL trials; HEPATOCELLULAR carcinoma; LONGITUDINAL method; PATIENT safety; PROTEINS; SURVIVAL; DESCRIPTIVE statistics; CHEMICAL inhibitors
- Publication
Oncologist, 2017, Vol 22, Issue 7, p780
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1634/theoncologist.2017-0058