title: Trebananib (AMG 386) in Combination With Sunitinib in Patients With Metastatic Renal Cell Cancer: An Open-Label, Multicenter, Phase II Study.
abstract: OBJECTIVE
  Trebananib, an investigational recombinant peptide-Fc fusion protein, neutralizes the receptor-ligand interaction between Tie2 and angiopoietin-1/2. This phase II study was conducted to evaluate trebananib plus sunitinib, a vascular endothelial growth factor receptor inhibitor, in patients with metastatic clear cell renal cell carcinoma.
  
  
  METHODS
  Adults with metastatic renal cell carcinoma were enrolled sequentially onto two cohorts that received sunitinib 50 mg once per day for 4 weeks on and 2 weeks off and intravenous trebananib once per week at a dose of 10 mg/kg in cohort A or 15 mg/kg in cohort B. The primary end points were incidences of adverse events (AEs) and dose interruptions of sunitinib during the first 12 weeks of treatment. Secondary end points included objective response rate and progression-free survival.
  
  
  RESULTS
  Eighty-five patients were enrolled: 43 in cohort A, and 42 in cohort B. During the first 12 weeks of treatment, 58% and 57% of patients in cohorts A and B, respectively, had sunitinib dose interruptions (dose decrease, withholding, or withdrawal). The most frequent AEs were diarrhea (cohort A, 74%; cohort B, 67%), mucosal inflammation (cohort A, 49%; cohort B, 60%), and hypertension (cohort A, 52%; cohort B, 45%). AEs of grade 3 or greater occurred in 58% of patients in cohort A and in 69% of patients in cohort B. The objective response rate was 58% and 63% in cohorts A and B, respectively. The median progression-free survival time was 13.9 months (95% CI, 10.4 to 19.2) and 16.3 months (95% CI, 13.1 to 21.4) in cohorts A and B, respectively. The median overall survival time was 36 months (95% CI, 25.2 to not estimable) in cohort A and was not estimable (median follow-up, 25 months) in cohort B.
  
  
  CONCLUSIONS
  Trebananib plus sunitinib seemed to increase toxicity at the tested doses. Efficacy results suggest a potential benefit for the addition of trebananib to sunitinib.
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA. mba41@georgetown.edu.
authors: Michael B
authors: MB
authors: Atkins
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
authors: Gwenaelle
authors: G
authors: Gravis
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
authors: Kazimierz
authors: K
authors: Drosik
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
authors: Tomasz
authors: T
authors: Demkow
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
authors: Piotr
authors: P
authors: Tomczak
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
authors: Shirley S
authors: SS
authors: Wong
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
authors: M Dror
authors: MD
authors: Michaelson
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
authors: Toni K
authors: TK
authors: Choueiri
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
authors: Benjamin
authors: B
authors: Wu
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
authors: Lynn
authors: L
authors: Navale
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
authors: Douglas
authors: D
authors: Warner
authors: Michael B. Atkins, Georgetown University, Washington, DC; Gwenaelle Gravis, Institut Paoli Calmettes, Marseille; Alain Ravaud, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux, France; Kazimierz Drosik, Regional Cancer Center, Opole; Tomasz Demkow, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw; Piotr Tomczak, University of Medical Sciences, Poznan, Poland; Shirley S. Wong, Western Hospital, Footscray, Victoria, Australia; M. Dror Michaelson, Massachusetts General Hospital; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; and Benjamin Wu, Lynn Navale, and Douglas Warner, Amgen, Thousand Oaks, CA.
authors: Alain
authors: A
authors: Ravaud
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000077210:Sunitinib
chemical_list: D007211:Indoles; D011758:Pyrroles; D011993:Recombinant Fusion Proteins; D000077210:Sunitinib; C551398:trebananib