title: Progression free survival of first line vascular endothelial growth factor-targeted therapy is an important prognostic parameter in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  Intrinsic resistance in metastatic renal cell carcinoma (mRCC) was recently associated with poor overall survival (OS), suggesting that VEGF inhibitor sensitivity may represent a valuable prognostic marker. We explored the duration of progression free survival (PFS) in first-line treatment and other variables as prognostic markers in mRCC.
  
  
  METHODS
  Medical records from 119 mRCC patients receiving first line treatment with tyrosine kinase inhibitors (TKI) were retrieved retrospectively. Kaplan-Meier and log-rank analyses were employed on PFS and OS and multivariate Cox proportional hazard model analysed clinical parameters for their prognostic relevance.
  
  
  RESULTS
  The median PFS of first line treatment was 8.4 months (95% confidence interval 5.8-11) associated with a median OS of 28.2 months (95% CI 20.9-35.4). Second line therapy with another TKI or mTOR-inhibitor was applied to 81 patients (68%). PFS of any second line therapy was 5.1 and 3.7 months in first line treatment responders and non-responders (p = 0.3), respectively. Univariate analyses revealed bone metastases, prior cytokine treatment, Memorial Sloan Kettering cancer centre (MSKCC) score, objective response rate, Eastern Cooperative Oncology Group (ECOG) performance status, first line PFS with 6 months taken as cut-off parameter and second line treatment as prognostic variables. Multivariate analyses proved first line PFS above 6 months (95% CI 0.154-0.641; HR 0.314), second line treatment (95% CI 0.162-0.657; HR 0.326), MSKCC score (95% CI 1.07-3.392; HR 1.905) and objective response rate (95% CI 0.358-0.989; HR 0.595) to be independent prognostic markers.
  
  
  CONCLUSIONS
  The duration of first line PFS is an independent prognostic variable but not predictive for subsequent therapy.
authors.affiliation: Department of Hematology, Hemostatis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Seidel
authors.forename: Jonas
authors.initials: J
authors.lastname: Busch
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
authors.forename: Sandra
authors.initials: S
authors.lastname: Steffens
authors.forename: Martin
authors.initials: M
authors.lastname: Fenner
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A