Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Pharmacodynamic Biomarker for Pazopanib in Metastatic Renal Carcinoma

Clin Genitourin Cancer. 2017 Apr;15(2):207-212. doi: 10.1016/j.clgc.2016.08.011. Epub 2016 Aug 17.

Abstract

Introduction/background: Traditional imaging assessment criteria might not correlate well with clinical benefit from vascular endothelial growth factor pathway-directed therapy in metastatic renal cancer. Preclinical data suggest tumor growth is preceded by a rise in Ktrans level, a parameter derived from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) that reflects vascular permeability. We thus hypothesized that Ktrans might be a predictive biomarker for pazopanib.

Patients and methods: Patients with metastatic renal cancer were treated with pazopanib at 800 mg oral daily until disease progression. MRI of the abdomen and pelvis with a DCE-MRI sequence was obtained at baseline and every 8 weeks.

Results: Seventy-three DCE-MRI scans were completed and 66 were technically assessable. Of the 17 patients with at least 1 DCE-MRI scan after the baseline scan, 16 (94%) had a decline in Ktrans level. Changes in Ktrans compared with baseline after 1, 8, 16, and 24 weeks were -49%, -65%, -63%, and -53%, respectively (P = .0052, repeated measures analysis of variance). The median Ktrans nadir occurred at 8 weeks. The median progression-free survival (PFS) was 32.1 weeks. PFS was longer in patients with higher baseline Ktrans values (P = .036, log rank). Baseline Ktrans did not reach significance in a Cox proportional hazard model including clinical prognostic index and previous treatments (P = .083).

Conclusion: We show that Ktrans is a pharmacodynamic biomarker for pazopanib therapy in metastatic renal cancer. Because of the small sample size, the predictive capacity of Ktrans recovery could not be assessed, but baseline Ktrans correlated with PFS.

Trial registration: ClinicalTrials.gov NCT01599832.

Keywords: DCE-MRI; K(trans); Progression; Renal cancer; VEGF receptor tyrosine kinase.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / pharmacology
  • Contrast Media / administration & dosage
  • Disease Progression
  • Female
  • Humans
  • Kidney Neoplasms / diagnostic imaging*
  • Kidney Neoplasms / drug therapy*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Pyrimidines / administration & dosage*
  • Pyrimidines / pharmacology
  • Sulfonamides / administration & dosage*
  • Sulfonamides / pharmacology
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Contrast Media
  • Pyrimidines
  • Sulfonamides
  • pazopanib

Associated data

  • ClinicalTrials.gov/NCT01599832