Clinical decision-making for immunotherapy in metastatic renal cell carcinoma

To review the treatment options in metastatic renal cell carcinoma (mRCC) in the light of new immunotherapy results.

Second-line treatment strategies for treatment of mRCC after progression on first-line VEGF-targeted therapy have recently undergone a major change. Treatment guidelines currently recommend the use of either nivolumab, a programmed cell death 1 (PD-1) inhibitor, or cabozantinib, an inhibitor of multiple receptor tyrosine kinases, as preferred choices. Many factors influence the decision, but there are no predictive markers to guide the choice. It is not known at what stage, it is most appropriate to offer a checkpoint inhibitor (CPI) such as nivolumab; various factors influence this decision including the adverse event profile and the age of the patient. Recent positive first-line trial results with cabozantinib, with the combination of two CPIs (a PD-1-PD-L1 inhibitor and a CTLA-4 inhibitor) and with a CPI with a VEGF inhibitor suggest that the first-line treatment paradigm will change rapidly, with consequential changes in second-line recommendations.

The treatment landscape in mRCC is changing rapidly and recent trial results suggest that CPI treatment combined with either another CPI or a VEGF inhibitor may be appropriate as first-line therapy in the future.