New Perspectives: An Oral Multikinase Inhibitor in Patients with Advanced RCC

Sorafenib (Nexavar®; Bayer Healthcare, West Haven, CT, USA) is an oral multikinase inhibitor that may provide dual action by inhibiting tumour cell proliferation and angiogenesis. Sorafenib was recently evaluated in the largest phase 3, randomised trial ever conducted in renal cell carcinoma (RCC): Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET). In TARGET, sorafenib significantly increased progression-free survival versus placebo, which led to a change in the study protocol allowing patients in the placebo arm of the trial to cross over to receive sorafenib. At the time of crossover, sorafenib improved overall survival by 39% compared with placebo (hazard ratio = 0.72; 95% confidence interval 0.54–0.94; p = 0.02, not significant as per O’Brien–Fleming threshold for statistical significance: p = 0.0005). Sorafenib continued to show a trend towards improved overall survival at a subsequent analysis 6 mo post-crossover. Importantly, 84% of sorafenib-treated patients achieved investigator-assessed stable disease or better compared with 55% of placebo recipients. Sorafenib was well tolerated, had a manageable side-effect profile, and offered benefit with no compromise in quality of life. The data from the phase 3 TARGET study provided further evidence that sorafenib may be effective in a wide range of patients with advanced RCC. Clinical trials are planned to assess the potential of sorafenib as combination therapy and in the adjuvant setting.