Long-term safety of sorafenib (SOR) for the treatment (tx) of advanced clear-cell renal-cell carcinoma (RCC): Data analysis from patients (pts) treated for over 1 year in the phase III TARGET study

Abstract

e16057 Background: Results of the phase III multicenter TARGET study, a randomized, double-blind, placebo (PBO)- controlled study of tx with SOR in pts with clear-cell RCC in whom 1 prior systemic therapy had failed, indicated that SOR is effective (PFS 5.5 vs 2.8 mo, HR=0.44, P<0.000001, and 39% increase in survival for SOR vs PBO, HR=0.71, P=0.015) and safe in pts with advanced RCC (Escudier et al. N Engl J Med. 2007). With a database cut-off of Sept 8, 2006, we analyzed the safety of long-term use of SOR in pts in TARGET (study start Nov 2003). Methods: Pts (N=903) with advanced metastatic clear-cell RCC that had progressed after 1 systemic tx, ECOG PS 0–2, and low- or intermediate-risk MSKCC score were randomized 1:1 to SOR 400 mg BID or PBO. End points included OS, PFS, and safety. A single planned analysis of PFS showed a significant benefit of SOR over PBO; consequently, pts assigned to PBO were offered SOR. Descriptive analysis of safety and efficacy of pts treated >1 year (y) was conducted. Results: 169/903 pts were randomized to SOR and treated >1 y and 27 pts treated >2 y. Due to crossover of PBO to SOR, only 6 pts randomized to PBO were treated with SOR >1 y. Pts treated with SOR >1 y had median PFS of 10.9 months and a response rate of 22.5%. Median tx duration was 20 months. Drug-related adverse events (AEs) were mainly grades 1 and 2 and occurred early during tx (see Table ); 31% and 22% of pts required dose interruption and reduction, respectively, because of AEs. Conclusions: Long-term tx with SOR did not result in new toxicities or an increase in overall incidence of tx-related AEs. Toxicity was not cumulative and no increase in grades 3/4 AEs was observed. Pts with preexisting cardiac disease or hypertension tolerated long-term tx with SOR; no dose reduction was required. No increase in cardiovascular toxicity was observed in this pt population. Long-term tx of pts with advanced RCC with SOR is medically manageable, with a predictable AE profile. [Table: see text] [Table: see text]