title: A phase 2, single-arm study of ramucirumab in patients with metastatic renal cell carcinoma with disease progression on or intolerance to tyrosine kinase inhibitor therapy.
abstract: BACKGROUND
  Multitargeted tyrosine kinase inhibitors (TKIs) have antitumor activity in metastatic renal cell carcinoma (mRCC). Resistance to these agents develops frequently, and their use is often limited by intolerance. Ramucirumab is a recombinant human monoclonal antibody directed against human vascular endothelial growth factor receptor-2. For this study, the authors investigated the clinical efficacy and safety of ramucirumab in patients with TKI-resistant/intolerant mRCC.
  
  
  METHODS
  In this single-arm phase 2 trial, patients received ramucirumab 8 mg/kg every 2 weeks until they developed disease progression or intolerable toxicity. The primary endpoint was the best objective response rate (ORR); additional endpoints included the disease control rate (DCR), progression-free survival (PFS), the median duration of overall response, and safety.
  
  
  RESULTS
  Thirty-nine patients with RCC received ramucirumab monotherapy. Prior TKI therapy included sunitinib (59% of patients), sunitinib and sorafenib (30.8% of patients), and sorafenib (10.3% of patients). The ORR was 5.1% (95% confidence interval [CI], 0.6%-17.3%). The 12-week DCR was 64.1% (95% CI, 47.2%-78.8%). The median PFS was 7.1 months (95% CI, 4.1-9.7 months), and the median overall survival was 24.8 months (95% CI, 18.9-32.6 months). Grade 3 or higher adverse events that occurred in ≥5% of patients included grade 3 hypertension (7.7%) and proteinuria (5.1%). There was 1 on-study death from multiorgan failure.
  
  
  CONCLUSIONS
  Although the study did not meet its primary endpoint of ≥15% ORR, ramucirumab was associated with evidence of antitumor activity in patients with TKI-resistant/intolerant mRCC. Ramucirumab was safe and well tolerated.
authors.affiliation: Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Garcia
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hudes
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Laura S
authors.initials: LS
authors.lastname: Wood
authors.forename: Jayne
authors.initials: J
authors.lastname: Gurtler
authors.forename: Shailender
authors.initials: S
authors.lastname: Bhatia
authors.forename: Adarsh
authors.initials: A
authors.lastname: Joshi
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Hozak
authors.forename: Yihuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Schwartz
authors.forename: John A
authors.initials: JA
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2; D000096662:Ramucirumab
keywords: metastatic; monoclonal antibody; phase 2; ramucirumab; renal cell carcinoma