Ep. 5: Optimizing Sequential Therapy in Advanced RCC

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

December 11, 2025

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Key Points

  • Tyrosine kinase inhibitors (TKIs) approved for second-line renal cell carcinoma (RCC) have different toxicity profiles.

  • Patients should be educated on and open about side effects so treatment can be optimized for long-term tolerability.

  • Second-line treatment selection must consider prior therapies and the current disease progression.

Core Considerations for Treating Advanced RCC 

The hosts of the Oncology Brothers podcast—Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center—were joined by three RCC experts, 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, to shared their core treatment paradigms for patients with relapsed or refractory RCC.

The available TKIs for second-line RCC have distinct toxicity profiles, and balancing efficacy against tolerability is a driving factor in treatment selection and dose optimization. Oncologists should proactively educate patients on potential side effects for each TKI and emphasize that dose reductions may be necessary for long-term success, said Dr. Braun.

In RCC, TKI dose intensity matters, so patients should start at the highest standard dose. Transparency between patients and oncologists regarding side effects and symptoms is crucial for shared decision-making and treatment customization, said Dr. Vaishampayan. 

Choosing treatments in the second-line and beyond absolutely depends on what patients received in the front-line, how they tolerated it, and the progression of their disease. There is no “right answer” for all patients, so individual patient preferences and treatment logistics may matter even more, said Dr. McGregor.

In closing, the doctors noted that ongoing trials such as STRIKE and PROBE, as well as new trials evaluating novel agents and combination regimens, could shift the treatment landscape across all lines of therapy in RCC.