Sunitinib in the treatment of metastatic renal cell carcinoma.

Sunitinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that targets various receptors, including vascular endothelial growth factor receptors (VEGFRs). Sunitinib received approval in 2006 and became a standard treatment option in the first-line treatment of metastatic renal cell cancer (mRCC) after a phase III trial showed superiority compared with interferon alpha (IFN-α). Sunitinib has also shown activity in second-line treatment in several trials. Most of the combination trials with sunitinib with various agents have led to considerable toxicity without improving efficacy. Sunitinib alone causes significant side effects and has a distinct profile with diarrhoea, hypertension, skin effects hypothyroidism, fatigue and nausea of special interest. The recommended dose of sunitinib in mRCC is 50 mg orally daily for 4 weeks, followed by 2 weeks off treatment (4/2 schedule). An alternative 2 weeks on, 1 week off schedule (2/1 schedule) seems to be of similar efficacy and better tolerability and could be more widely used in the future. An intermittent treatment strategy with a stop in remission and re-induction after progression showed efficacy in smaller trials and is currently being evaluated in a phase III trial. Direct comparison of sunitinib with pazopanib in first-line treatment showed a similar efficacy for both TKIs with a distinct toxicity profile. Data from two phase II trials showed that sunitinib has also activity in non-clear cell cancer and is an option due to a lack of better alternatives. Currently, after immune checkpoint inhibitors have shown very promising results in the second-line treatment of RCC, they are being tested in a number of phase III trials in the first-line setting. The future will show the position of sunitinib in the first-line treatment of RCC in the era of the immune checkpoint inhibitors.