Systemic therapy of metastatic renal cell carcinoma

Background. Patients with metastatic renal cell carcinoma (RCC) have an unfavorable and limited prognosis. Nevertheless, the prognosis could be improved in recent years by so-called targeted therapy. Results. In total seven new agents, such as tyrosine kinase inhibitors (TKI), mammalian target of rapamycin (mTOR) inhibitors and the vascular endothelial growth factor (VEGF) antibody bevacizumab have been approved for metastatic RCC and led to a prolongation of progression-free survival (PFS) and a median overall survival of 2-3 years. For first line therapy, the TKIs sunitinib and pazopanib as well as the combination of bevacizumab and interferon-alpha (IFN alpha) and temsirolimus for poor risk patients only are now approved. Sunitinib and pazopanib, which are restricted for use in cytokine pretreated patients, may also be administered in the second line. Axitinib compared with sorafenib improved PFS in patients pretreated with cytokines or sunitinib. Additional options in the second line or beyond are everolimus and sorafenib. Discussion. The availability of new targeted agents has significantly improved the outcome and prognosis of metastatic RCC. Despite phase III trials investigating the optimal therapy sequence this has not yet been clarified due to the lack of predictive factors. Possible interesting new therapeutic options could emerge with immune check point inhibitors.