Sequential FDG-PET/CT as a biomarker of response to Sunitinib in metastatic clear cell renal cancer

Clin Cancer Res. 2011 Sep 15;17(18):6021-8. doi: 10.1158/1078-0432.CCR-10-3309. Epub 2011 Jul 8.

Abstract

Purpose: To test the hypothesis that sequential (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is a correlative marker in metastatic clear cell renal cancer (mRCC), patients were treated with sunitinib. Three sequential scans were conducted to determine whether the timing of the investigation was relevant.

Experimental design: Forty-four untreated mRCC patients were enrolled into this prospective phase II study. (18)F-FDG-PET/CT scans were conducted before (n = 44) and after 4 weeks (n = 43) and 16 weeks (n = 40) of sunitinib given at standard doses. The primary endpoint was to correlate FDG-PET/CT response (20% reduction in SUV(max)) at 4 and 16 weeks with overall survival (OS).

Results: Forty-three (98%) patients had FDG-PET/CT avid lesions at diagnosis (median SUV(max) = 6.8, range: <2.5-18.4). In multivariate analysis, a high SUV(max) and an increased number of PET-positive lesions correlated with shorter OS [HR: 3.30 (95% CI: 1.36-8.45) and 3.67 (95% CI: 1.43-9.39), respectively]. After 4 weeks of sunitinib, a metabolic response occurred in 24 (57%) patients, but this did not correlate with progression-free survival (HR for responders = 0.87; 95% CI: 0.40-1.99) or OS (HR for responders = 0.80; 95% CI: 0.34-1.85). After 16 weeks of treatment, disease progression on FDG-PET/CT occurred in 28% (n = 12) patients which correlated with a decreased OS and PFS [HR = 5.96 (95% CI: 2.43-19.02) and HR = 12.13 (95% CI: 3.72-46.45), respectively].

Conclusions: Baseline FDG-PET/CT yields prognostic significant data. FDG-PET/CT responses occur in the majority of patients after 4 weeks of therapy; however, it is not until 16 weeks when the results become prognostically significant.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Renal Cell / diagnostic imaging*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Female
  • Fluorodeoxyglucose F18*
  • Humans
  • Indoles / therapeutic use*
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / diagnostic imaging*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Multimodal Imaging*
  • Neoplasm Metastasis
  • Positron-Emission Tomography*
  • Prognosis
  • Pyrroles / therapeutic use*
  • Sunitinib
  • Tomography, X-Ray Computed*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Fluorodeoxyglucose F18
  • Sunitinib