Ep. 4: Second-Line RCC Management: Tolerability, Comorbidities, and Long-Term Planning

Ulka Vaishampayan, MBBS University of Michigan | Bradley McGregor, MD Dana-Farber Cancer Institute | David Braun, MD, PhD Yale School of Medicine | Rahul Gosain, MD, MBA Wilmot Cancer Institute | Rohit Gosain, MD Roswell Park Comprehensive Cancer Center

December 10, 2025

Copy Link Share
Key Points

  • Response to tyrosine kinase inhibitors (TKIs) is dose-dependent in renal cell carcinoma (RCC).

  • With TKIs other than tivozanib, most patients will require dose reductions.

  • Patient education on dose optimization is key to finding a stable dose that can be tolerated long-term.

TKI Dose Reductions in Relapsed or Refractory RCC

In contrast to other cancers, where dose reductions do not appear to compromise efficacy, relapsed or refractory RCC shows a dose-dependent response to TKIs. However, dose reductions for toxicity will be required in many patients. Medical oncologists, Bradley McGregor, MD, of Dana-Farber Cancer Institute, David Braun, MD, PhD, of Yale School of Medicine, and Ulka Vaishampayan, MBBS, of University of Michigan, discussed how to balance these conflicting data in practice.

The panel agreed that it’s most effective to start at the highest dose for each TKI, then reduce from there to find a dose that patients can tolerate. Patients should be educated that dose reductions with TKIs other than tivozanib are expected in most patients, so they don’t try to weather a higher dose that requires more interruptions, which may reduce total exposure. Paradoxically, pausing for toxicities and quickly lowering the dose to find a stable dose is the best path to maintaining dose intensity long-term, said Dr. McGregor. 

“The key is proactive counseling,” Dr Braun said. “I think patients are worried about telling their side effects to their physician, it’s not a failure if we have to reduce the dose, the expectation is that will happen, but we don’t know what the right dose is for you.”

Compared to the other TKIs, tivozanib showed a much lower rate of reduction due to toxicity in trials. Tivozanib also has a distinct schedule of 3 weeks of daily dosing followed by a 1-week break, which may contribute to the more favorable tolerability, Dr. Vaishampayan said. For tivozanib, both the dose and the on-treatment period of each cycle can be adjusted to individualize therapy.