Combination or sequencing strategies to improve the outcome of metastatic renal cell carcinoma patients: a critical review

The introduction of novel anti-angiogenic therapies has greatly improved the outcome of patients with metastatic renal cell carcinoma (mRCC). The use of these therapies in combination or sequentially is proposed to provide greater efficacy. We have reviewed completed and ongoing clinical trials in mRCC that have reported efficacy and/or safety data of novel therapies used in combination or sequentially. Bevacizumab appears to be a useful partner when combined with interferon (IFN), while controversial results have been reported when combined with temsirolimus and everolimus. Other combinations appear to have unacceptable tolerability or require dose or schedule optimization. Sequencing data provide a clear indication that multiple lines of treatment may extend survival. The 'ideal' sequence, however, is still unknown. In conclusion, novel therapies used in combination or sequentially have potential to provide optimised treatment and patient outcomes in mRCC. The results from ongoing/planned trials are expected to help shape future therapy.