Landmark Trials In Renal Cancer

The therapy of kidney cancer has made multiple major advances. Eleven agents are now approved by FDA for treatment of metastatic RCC and one agent is approved for adjuvant therapy for localized high risk disease post nephrectomy. In addition the trials addressing the role of surgery also represent major strides in therapy. All these advances in RCC therapeutics have occurred through clinical trials. This paper is a summary of landmark trials that have been critical in the therapeutic development journey in advancing the care and improving outcomes in kidney cancer. The front line therapies are summarized starting with immunotherapy with high dose interleukin-2 to targeted therapies such as bevacizumab (monoclonal antibody), receptor tyrosine kinases such as sorafenib, sunitinib, and pazopanib and MTOR inhibitors lke temsirolimus in the front line setting. Recently the combinations of ipilimumab and nivolumab as well as bevacizumab and atezolizumab have demonstrated promising efficacy in metastatic disease and these regimens are likely to receive FDA approval. In second line and beyond, therapies such as everolimus, nivolumab, lenvatinib+ everolimus and Cabozantinib have proven benefit. Adjuvant post nephrectomy trials have been conducted with conflicting results. Majority have shonwn lack of benefit, however one study conducted in T3/T4/N1 disease revealed statistically significant disease free survival favoring ajuvant sunitinib therapy leading to FDA approval. This paper summarizes the data from the reported trials and discusses recent developments in RCC therapeutics.