Treatment of metastatic renal cell carcinoma in second and further lines

In the era of cytokines, the median survival of patients with metastatic renal cell carcinoma (mRCC) was on average approximately 10 months.

Since the year 2005, we have witnessed major progress in the treatment of mRCC. Currently, a total of seven agents for targeted biological therapy

for the treatment of mRCC are registered by the European Medicines Agency (EMA). They are antiangiogenic agents targeted at the pathway of

the vascular endothelial growth factor (VEGF), which include tyrosine kinase inhibitors (TKIs) of the VEGF receptor, such as sunitinib, sorafenib,

pazopanib, and axitinib, as well as a monoclonal antibody against the VEGF receptor – bevacizumab. Temsirolimus and everolimus are designed to

inhibit the mTOR pathway. Sequential therapy, which employs the administration of several different agents in a prescribed sequence, can extend

the duration of progression-free survival (PFS) for over two years, and the overall survival even longer. The second line of treatment involves the use

of sorafenib, but also sunitinib and pazopanib after failure of cytokines, as well as everolimus in the second or third line of treatment after failure

of TKIs or bevacizumab. As yet, axitinib is the last to have been registered in the second line of treatment after failure of cytokines, TKIs as well as

temsirolimus. After failure of everolimus in the second line, confirmation of the efficacy of other TKIs in the further line of treatment is expected.

Keywords: metastatic renal cell carcinoma, targeted therapy, sequential therapy, multikinase inhibitors, mTOR inhibitors