Considerations for the design of future clinical trials in metastatic renal cell carcinoma.

Metastatic renal cell carcinoma (mRCC) remains incurable in most cases, and there is a need to improve outcomes through clinical research, which will include development of novel molecularly targeted or immunotherapeutic agents. There are also many remaining questions regarding the optimization of currently available regimens, including the utility of dose escalation, the benefit of combination therapy, and the optimal sequences of therapies. Addressing these clinical questions will require careful planning and the inclusion of novel elements in trial designs. Future trials should include molecular phenotyping and selection of patients most likely to benefit from targeted therapies. In this article, we consider lessons learned from previous trials in mRCC and discuss how these lessons might be implemented in the design of future trials that focus on clinically useful questions and provide results that can be readily interpreted. The ultimate aim of the next generation of mRCC trials will be rapid cost-effective identification, testing, and approval of agents that can improve prognosis in this challenging disease.