Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a biomarker for the effect of PTK787/ZK 222584 (PTK/ZK) as second-line mono-therapy in patients with stage IIIB or stage IV non-small cell lung cancer (NSCLC)

Abstract

7676 Background: Overexpression of vascular endothelial growth factor receptor (VEGF-R) in NSCLC-tumors is linked to poor prognosis and shorter overall survival. PTK/ZK (PTK/ZK) is a novel, oral, anti-angiogenic compound blocking all currently known VEGF receptors (VEGF-R1–3). DCE-MRI measures early changes in tumour-associated vasculature in response to treatment and has been successfully used as a biomarker for biological activity of PTK/ZK in liver metastases from colorectal cancer. Methods: This is a prospective, multi- centre, phase-II study of PTK/ZK in pretreated patients with advanced stage NSCLC. 54 patients (pts) received 1,250 mg PTK/ZK once daily (qd), followed by 58 patients receiving 1,250 mg (500 am + 750 mg pm) PTK/ZK twice daily (bid). Response evaluation was based on RECIST. Disease stabilization of at least 12 weeks based on CT/MRI-imaging was defined as clinically relevant drug activity. DCE-MRI was performed 2- 4 hours after PTK/ZK administration, on day 2 and at day 28. Contrast enhancement for the whole tumour was assessed by calculating the transfer constant (Ktrans) using a two-compartment model. Results: DCE-MRI was performed successfully in 35 pts in the qd cohort on day 2 and 29 pts in the qd cohort at day 28. There was a statistically significant mean reduction in Ktrans at day 2 of 35.2 % (p<0.0001, N=35, paired ‘t’ test) and at Day 28 of 38.1% (p<0.0001, N=29). 32 pts with day 2 DCE- MRI were evaluable for response assessment with 10 (31%) achieving SD at 12 weeks and 22 (69%) with progressive disease (PD). Both the SD group and the PD group had significant mean reductions in Ktrans at day 2 (39.4% and 37.1%, respectively). However, the difference between SD and PD was not statistically significant. Data for the bid cohort will be presented at the meeting. Conclusions: PTK/ZK causes statistically significant reduction in tumour vascular parameters of lung tumours. Ktrans has previously been shown to correlate with clinical outcome. However, for the qd cohort, no correlation could be demonstrated. This may be due to the limitation of the sample size as well as the heterogeneity of the targeted lesions selected for this study. [Table: see text]

Antiangiogenic Agents and Vascular Disrupting Agents for the Treatment of Lung Cancer: A Review

“…100 Another phase II trial in pretreated NSCLC using dynamic contrast-enhanced magnetic resonance imaging showed a statistically significant reduction in tumor vascular parameters. 101 Pazopanib (GW786034) was tested in patients with stage I/II NSCLC treated for 2 to 6 weeks before surgery. Twenty of 23 patients (87%) had reduction of the tumor volume, and three had partial response.…”