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

作者：Sweis Randy F; Medved Milica; Towey Shannon; Karczmar Gregory S; Oto Aytekin; Szmulewitz Russell Z; O'Donnell Peter H; Fishkin Paul; Karrison Theodore; Stadler Walter M^*

来源：Clinical Genitourinary Cancer, 2017, 15(2): 207-212.

DOI：10.1016/j.clgc.2016.08.011

• DCE-MRI
• K-trans
• Progression
• Renal cancer
• VEGF receptor tyrosine kinase

Metastatic renal cancer is commonly treated with drugs that block tumor blood vessel growth, such as pazopanib. Response often cannot be determined accurately using standard imaging scans. In this study, we evaluated patients with a magnetic resonance imaging parameter that reflects tumor blood vessel changes. It declined consistently after treatment, and higher baseline values correlated with longer time to disease progression.
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 K-trans 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 K-trans level. Changes in K-trans 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 K-trans nadir occurred at 8 weeks. The median progression-free survival (PFS) was 32.1 weeks. PFS was longer in patients with higher baseline K-trans values (P = .036, log rank). Baseline K-trans did not reach significance in a Cox proportional hazard model including clinical prognostic index and previous treatments (P = .083). Conclusion: We show that K-trans is a pharmacodynamic biomarker for pazopanib therapy in metastatic renal cancer. Because of the small sample size, the predictive capacity of Kt's recovery could not be assessed, but baseline K-trans correlated with PFS.

• 出版日期2017-4