Expert Highlights Armamentarium of Advanced Kidney Cancer Therapies

An expert from the University of Texas Southwestern Medical Center discusses several phase 3 clinical trials supporting the use of various single-agent and combination immunotherapy regimens for advanced kidney cancer.

During the 2023 Genitourinary Cancers Symposium, CancerNetwork® spoke with Tian Zhang, MD, MHS, about data from several phase 3 clinical trials that have shaped the current treatment landscape for advanced kidney cancer.

Zhang, an associate professor in the Department of Medicine at Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, highlighted how the studies have led to each regimen’s FDA approval, with treatment options ranging from immunotherapy combinations to single-agent VEGF-tyrosine kinase inhibitors (TKIs).


In refractory clear cell kidney cancer, we have multiple treatment options approved. These include everolimus [Afinitor], axitinib [Inlyta], nivolumab [Opdivo], and cabozantinib [Cabometyx] all as monotherapies and the combination of lenvatinib [Lenvima] with everolimus. As our immunotherapy options have improved in the first-line setting, we now also have a single agent called tivozanib [Fotivda] in the refractory setting.

We touched on the phase 3 trials that have led to these approvals for refractory disease. The randomized phase 3 AXIS trial [NCT00678392] for axitinib vs sorafenib [Nexavar] gained axitinib approval in the refractory setting, showing a median progression-free survival of about 6.7 months.1

The phase 3 METEOR trial [NCT01865747] was the registrational trial for cabozantinib to gain its first label in refractory/metastatic renal cell carcinoma. Cabozantinib was compared [with] everolimus in that setting, with a median progression-free survival interval of about 7.4 months.2

You’ll notice that in the refractory setting, most of these trials and approvals are hedged on improving median progression-free survival.

The most recent VEGF TKI to be approved in this setting, tivozanib, was approved based on the phase 3 TIVO-3 trial [NCT02627963] of tivozanib [Fotivda] vs sorafenib. Even though the median progression-free survival for tivozanib was 5.6 months, it was statistically significant when compared [with] sorafenib.3

Finally, we do have an immunotherapy approved as a monotherapy in the advanced setting for refractory renal cell carcinoma, and that’s nivolumab which gained its first approval in kidney cancer in the refractory setting based on the phase 3 CheckMate-025 trial [NCT01668784]. [It compared] nivolumab with everolimus with a medium PFS of 4.6 months, but it also improved median overall survival with a hazard ratio of 0.73.4

Based on this, we have multiple options now currently available as standard-of-care treatments in the refractory/metastatic setting.


  1. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet Oncol. 2011;378(9807):P1931-1939. doi:10.1016/S0140-6736(11)61613-9
  2. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17(7):P917-927. doi:10.1016/S1470-2045(16)30107-3
  3. Rini BI, Pal SK, Escudier BJ, et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020;21(1):P95-104. doi:10.1016/S1470-2045(19)30735-1
  4. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803-1813. doi:10.1056/NEJMoa1510665
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