Maturing of Renal Cancer Therapeutics

Abstract

Until recently, options for treatment of metastatic renal cancer were limited. High-dose interleukin-2 leads to sustained nearcompleteresponsesinaminorityofpatients,butistootoxicformost. Interferon leads to occasional responses and was the historical treatment reference, 1 but the benefit is modest, and the quality of life impact significant. It is in this context that the current vascular endothelialgrowthfactor(VEGF)pathwayandmammaliantargetofrapamycin (mTOR) ‐directed agents were developed. The phase II studies of the VEGF pathway inhibitors bevacizumab, sorafenib, and sunitinib and the mTOR inhibitor temsirolimus for treatment of renal cancer were all conducted within the same time frame; however, their sponsors elected different pathways for regulatory approval. Temsirolimus was compared with interferon in the front-line setting, with inclusion of a third combination arm, and with a survival end point in patients with poor prognostic features. 2 By limiting the study to poor-risk patients, the sponsors had hoped that the end point would be reached more rapidly in the competitive marketplace of multiple agentsundergoingphaseIIIevaluation.Unfortunately,thisrestric