Sequencing tyrosine kinase inhibitors or immediately switching to mTOR inhibitors in advanced kidney cancer: A critical review

Since the approval of Sorafenib and Sunitinib, many advanced renal cell carcinoma (aRCC) patients have been empirically treated by using the two tyrosine kinase inhibitors (TKIs) in sequence with the aim of prolonging the stabilization of their disease. This strategy is supported by the results of few small prospective and several small retrospective studies, all indicating that there is limited or no cross-resistance between the two TKIs. On the other hand, data from the randomized, placebo-controlled, phase III RECORD-1 trial showed that the mTOR inhibitor Everolimus is as effective after one TKI as it is after both TKIs. In this review we comment all the available evidence on this important subject*irrespective of its formal relevance*critically discussing the results obtained so far, with the aim of helping us to make the best clinical decisions possible.