Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure

Nizar M Tannir, Yu-Ning Wong, Christian K Kollmannsberger, Marc S Ernstoff, David J Perry, Leonard J Appleman, Edwin M Posadas, Daniel Cho, Toni K Choueiri, Andrew Coates, Neeraj Gupta, Rajendra Pradhan, Jiang Qian, Jihong Chen, Frank A Scappaticci, Justin L Ricker, Dawn M Carlson, M Dror Michaelson, Nizar M Tannir, Yu-Ning Wong, Christian K Kollmannsberger, Marc S Ernstoff, David J Perry, Leonard J Appleman, Edwin M Posadas, Daniel Cho, Toni K Choueiri, Andrew Coates, Neeraj Gupta, Rajendra Pradhan, Jiang Qian, Jihong Chen, Frank A Scappaticci, Justin L Ricker, Dawn M Carlson, M Dror Michaelson

Abstract

Purpose: This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib.

Materials and methods: This open-label, multicentre, phase 2 trial of oral linifanib 0.25 mg/kg/day enrolled patients who had prior nephrectomy and adequate organ function. The primary end-point was objective response rate (ORR) per response evaluation criteria in solid tumors (RECIST) by central imaging. Secondary end-points were progression-free survival (PFS), overall survival (OS) and time to progression (TTP). Safety was also assessed.

Results: Fifty-three patients, median age 61 years (range 40-80) were enrolled (August 2007 to October 2008) across 12 North-American centres. Median number of prior therapies was 2 (range 1-4); 43 patients (81%) had clear-cell histology. ORR was 13.2%, median PFS was 5.4 months (95% Confidence Interval (CI): 3.6, 6.0) and TTP was the same; median OS was 14.5 months (95% CI: 10.8, 24.1). The most common treatment-related adverse events (AEs) were diarrhoea (74%), fatigue (74%) and hypertension (66%), and the most common treatment-related Grade 3/4 AE was hypertension (40%).

Conclusions: Linifanib demonstrated clinically meaningful activity in patients with advanced RCC after sunitinib failure. At 0.25 mg/kg/day, significant dose modifications were required. An alternative, fixed-dosing strategy is being evaluated in other trials.

Trial registration: ClinicalTrials.gov NCT00486538.