Progression free survival of first line vascular endothelial growth factor-targeted therapy is an important prognostic parameter in patients with metastatic renal cell carcinoma

Eur J Cancer. 2012 May;48(7):1023-30. doi: 10.1016/j.ejca.2012.02.048. Epub 2012 Mar 20.

Abstract

Purpose: 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.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / secondary
  • Disease-Free Survival
  • Female
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Prognosis
  • Protein Kinase Inhibitors / administration & dosage
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Vascular Endothelial Growth Factor A