Phase II study of first-line trebananib plus sorafenib in patients with advanced hepatocellular carcinoma Journal Article
| Authors: | Abou-Alfa, G. K.; Blanc, J. F.; Miles, S.; Ganten, T.; Trojan, J.; Cebon, J.; Liem, A. K.; Lipton, L.; Gupta, C.; Wu, B.; Bass, M.; Hollywood, E.; Ma, J.; Bradley, M.; Litten, J.; Saltz, L. B. |
| Article Title: | Phase II study of first-line trebananib plus sorafenib in patients with advanced hepatocellular carcinoma |
| 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 (power580% α50.20). 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. © AlphaMed Press. |
| Journal Title: | The Oncologist |
| Volume: | 22 |
| Issue: | 7 |
| ISSN: | 1083-7159 |
| Publisher: | Oxford University Press |
| Date Published: | 2017-07-01 |
| Start Page: | 780 |
| End Page: | e65 |
| Language: | English |
| DOI: | 10.1634/theoncologist.2017-0058 |
| PROVIDER: | scopus |
| PMCID: | PMC5507650 |
| PUBMED: | 28592620 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2017 -- Source: Scopus |
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