Evolving Treatment Options for Metastatic Renal Cell Carcinoma (mRCC)

Approximately a third of patients diagnosed with kidney cancer in the United States present with advanced disease and those who present with distant metastases historically had dismal 5-year relative survival. However, over the last several years, advancements have led to improved life expectancy and patient outcomes in those who develop advanced renal cell carcinoma. Metastatic clear cell renal cell carcinoma (mccRCC) treatment has rapidly evolved with multiple drug approvals since 2006. Moreover, multiple combination regimens including a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) plus immune checkpoint inhibitor (ICI) and the combination of ipilimumab plus nivolumab have supplanted first-line VEGF-TKI monotherapy. Thus, the insights we gained from prospective randomized controlled trials focusing on systemic therapy beyond first-line therapy in mRCC patients treated in the TKI monotherapy era quickly became less relevant with the adoption of contemporary first-line combination regimens. Herein, we will review contemporary first- and second-line therapies for mccRCC, as well as highly anticipated clinical trials looking into novel regimens beyond first-line therapy in patients who have received combination therapy.