BACKGROUND: Trebananib, an investigational peptibody, binds to angiopoietin 1 and 2, thereby blocking their interaction with Tie2.
PATIENTS AND METHODS: This open-label phase I study examined trebananib 3 mg/kg or 10 mg/kg intravenous (I.V.) once weekly plus sorafenib 400 mg twice per day or sunitinib 50 mg once per day in advanced RCC. Primary end points were adverse event incidence and pharmacokinetics.
RESULTS: Thirty-seven patients were enrolled. During trebananib plus sorafenib administration (n = 17), the most common treatment-related adverse events (TRAEs) included rash (n = 12; 71%), diarrhea (n = 12; 71%), hypertension (n = 11; 65%), and fatigue (n = 11; 65%); grade ≥ 3 TRAEs (n = 7; 41%); and 2 patients (12%) had peripheral edema. During trebananib plus sunitinib administration (n = 19), the most common TRAEs included diarrhea (n = 14; 74%), fatigue (n = 13; 68%), hypertension (n = 11; 58%), and decreased appetite (n = 11; 58%); grade ≥ 3 TRAEs (n = 13; 68%); and 8 (42%) patients had peripheral edema. Trebananib did not appear to alter the pharmacokinetics of sorafenib or sunitinib. No patient developed anti-trebananib antibodies. Objective response rates were 29% (trebananib plus sorafenib) and 53% (trebananib plus sunitinib).
CONCLUSION: The toxicities of trebananib 3 mg/kg or 10 mg/kg I.V. plus sorafenib or sunitinib in RCC were similar to those of sorafenib or sunitinib monotherapy, with peripheral edema being likely specific to the combinations. Antitumor activity was observed.
Written by:
Hong DS, Gordon MS, Samlowski WE, Kurzrock R, Tannir N, Friedland D, Mendelson DS, Vogelzang NJ, Rasmussen E, Wu BM, Bass MB, Zhong ZD, Friberg G, Appleman LJ. Are you the author?
Division of Cancer Medicine, Department of Investigational Cancer Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX; Pinnacle Oncology Hematology, Scottsdale, AZ; Comprehensive Cancer Centers of Nevada and US Oncology, Las Vegas, NV; Hillman Cancer Center, Pittsburgh, PA; Amgen Inc, Thousand Oaks, CA.
Reference: Clin Genitourin Cancer. 2013 Nov 13. pii: S1558-7673(13)00278-4.
doi: 10.1016/j.clgc.2013.11.007
PubMed Abstract
PMID: 24365125
Go "Beyond the Abstract" - Read an article written by the authors for UroToday.com
UroToday.com Renal Cancer Section
