Dr. Rini on the Current Standard of Care in R/R RCC

Brian I. Rini, MD, FASCO, Ingram professor of medicine, Division of Hematology Oncology, chief of Clinical Trials, Vanderbilt-Ingram University Cancer Center, on the current treatment landscape for patients with relapsed/refractory renal cell carcinoma (RCC).

As immune-oncology–based doublet combinations, such as nivolumab (Opdivo) plus cabozantinib (Cabometyx) or nivolumab plus ipilimumab (Yervoy), have become the standard of care in the frontline setting for patients with metastatic RCC, many patients who progress to the relapsed/refractory setting will have had prior exposure to immunotherapy, barring any contraindications, Rini says. Because of this shift in the frontline treatment of RCC, refractory RCC can now often be considered immune refractory RCC, Rini notes.

In the relapsed/refractory setting, the current standard of care is generally single-agent treatment with a VEGF TKI, Rini says. Various VEGF TKIs have demonstrated activity in the relapsed/refractory setting across different clinical trials; however, these studies were primarily conducted in the general refractory setting, rather that the TKI-refractory setting, Rini adds. Selection of a VEGF TKI in the relapsed/refractory setting typically comes down to a clinician’s familiarity with the agent, the drug’s toxicity profile, and patient preference, Rini explains.

Beyond the second-line setting, the phase 3 TIVO-3 trial (NCT02627963) evaluated tivozanib (Fotivda) vs sorafenib (Nexavar) in patients with relapsed/refractory RCC who received 2 or 3 prior lines of therapy. In March 2021, the FDA approved tivozanib for patients with relapsed/refractory advanced RCC following 2 or more prior systemic therapies, based on data from TIVO-3.

Notably, approximately one-quarter of the patients enrolled in TIVO-3 were immune refractory, Rini continues, adding that tivozanib demonstrated benefits compared with sorafenib. Although patients who were immune refractory represented a subset of patients on this trial, the data were extracted from an emerging, more modern population that received prior immunotherapy, Rini concludes.