Targeted Therapies for Renal Cell Carcinoma – More Gains from Using Them Again

Abstract

The development of molecularly targeted agents that inhibit pathways critical to the development of renal cell carcinoma has significantly improved outcomes in patients with these cancers. Compelling scientific and Phase III data has made the use of these agents the standard of care in the first-line treatment of these patients. There is now data to show that re-treating patients with other tyrosine kinase inhibitors is beneficial when they progress on sunitinib and/or sorafenib. A large Phase III trial recently showed that treatment with the mTOR inhibitor, everolimus, reduced the risk of progression by 70% (37% versus 65%) and increased median progression free survival (4 months versus 2 months) compared to placebo. Overall survival was not improved in this study, likely reflecting treatment crossover in the placebo arm. However, this data would position everolimus as the second-line standard of care. A consistent and growing body of literature would also suggest that re-treating with other kinase inhibitors (that the patient has not previously encountered) is a reasonable option. Use of second-line targeted therapy should not be deterred by the outcomes of initial treatment with sunitinib and/or sorafenib, as these do not appear to be predictive of outcomes with second-line therapy. However, in view of the poor absolute outcomes after second-line treatment and the benefits seen with rationally-developed targeted agents in the first-line setting, it would be preferable to enroll these patients in further trials.