Targeted
therapies have introduced a paradigm shift in the management of metastatic
renal cell carcinoma. Currently, four molecules (
sunitinib,
pazopanib,
bevacizumab plus
interferon,
temsirolimus) are considered in first-line
therapy, and three other molecules for second, or subsequent lines of
therapy (
everolimus,
axitinib,
sorafenib). In addition, other molecules and sequencing schemes are being tested in ongoing phase II/III studies. We conducted a systematic review using PubMed and several other databases up to December 2011 of prospective and retrospective studies on treatment management of metastatic
renal cell carcinoma using targeted
therapies, with a special focus on use of sequential treatment. Based on phase III data, the optimal sequencing scheme for patients with clear cell or even non-clear cell histological subtype appears to consist of
sunitinib, followed by
axitinib, followed by
everolimus. Subsequent treatment options rely on lower evidence studies and could consist of fourth-line
sorafenib or
sunitinib rechallenge. Such
therapies would qualify as last recourse options. In another context,
temsirolimus may be used in patients who fulfill the Memorial Sloan-Kettering
Cancer Center poor risk criteria or who have poor performance status. We conclude that in the current setting, sequential
therapy represents the cornerstone of effective management of metastatic
renal cell carcinoma.