title: Activity of single-agent bevacizumab in patients with metastatic renal cell carcinoma previously treated with vascular endothelial growth factor tyrosine kinase inhibitors.
abstract: OBJECTIVE
  The activity of systemic agents after progression when using vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibition (TKI) and mammalian target of rapamycin (mTOR) inhibition in patients with metastatic renal cell carcinoma (mRCC) is poorly characterized. The anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab has a broad US Food and Drug Administration label and National Comprehensive Cancer Network guideline level 2b recommendation in this setting; we thus explored our institutional experience in this population.
  
  
  METHODS
  We conducted a retrospective analysis of patients with mRCC who were treated with bevacizumab in the second- and/or third-line settings; the primary endpoint was progression-free survival (PFS). Overall response rates (ORR), overall survival (OS), and toxicity were analyzed.
  
  
  RESULTS
  Twenty-one patients were treated with bevacizumab: the median age was 63 years old; 80% were white and 14% were black; 80% had clear cell histology. All the patients had prior VEGFR TKI therapy; 43% had prior mTOR inhibitor; the median number of prior therapies was 3. The median PFS was 4.4 months (95% CI, 2.8-9.6 months), and the median OS was 19.4 months (95% CI, 9.9-NR months). ORR was 9.5%; 52% of subjects had stable disease as best response, and 52% had disease progression. For subjects treated with prior VEGF and mTOR inhibitors, median PFS and OS were 4.4 and 13.2 months, respectively. Grade 3 to 4 toxicities included fatigue (29%), dehydration (24%), failure to thrive (10%), constipation (10%), and muscle weakness (10%).
  
  
  CONCLUSIONS
  Single-agent bevacizumab has acceptable toxicity and moderate disease-stabilizing activity in selected patients with mRCC who have failed prior VEGFR TKI and mTOR inhibitors. These data support clinical benefit to continued ongoing VEGF inhibition. Further prospective studies of bevacizumab alone or with alternative targeted agents in previously treated populations with mRCC are warranted.
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Turnbull
authors.forename: Julien
authors.initials: J
authors.lastname: Cobert
authors.forename: Tracy
authors.initials: T
authors.lastname: Jaffe
authors.forename: Michael R
authors.initials: MR
authors.lastname: Harrison
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068258:Bevacizumab; C546842:MTOR protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases