Adjuvant Setting, Toxicity Considerations for Single-Agent, Combination nccRCC Therapy

A roundtable discussion, moderated by Laurence Albiges, MD, PhD, discussed the risk stratification and management of metastatic non-clear cell renal cell carcinoma (nccRCC), along with recent advancements in targeted therapies and immuno-agents, treatment sequencing and combination approaches, and adjuvant therapy options. Dr. Albiges was joined by Renée Maria Saliby, MD, MSc; Tian Zhang, MD; and Shahla Bari, MD.

In the fifth segment of the roundtable series, the panel weighs the progress and challenges in using pembrolizumab for adjuvant therapy in clear cell and nccRCC, emphasizing the need for more data on non-clear cell cases and addressing the toxicity profiles of IO/TKI regimens.

View the next segment on Future Directions in nccRCC: SAMETA, FORTUNE, and Second-Line Treatment.

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Dr. Albiges: We ought to move on to the question of the adjuvant setting. So here, once again, we had the chance to make progress, and we now have pembrolizumab as a standard of care that we are offering to our patients with adverse features, meaning they are at risk of relapse. However, this was conducted in clear cell cases. So, Dr. Zhang, do you offer adjuvant therapy to patients with nccRCC? Do we have data in that area?

Dr. Zhang: We have very minimal data. There has been maybe a handful of trials that have snuck under the radar. But, most of the data we have is for clear cell kidney cancer, particularly for adjuvant pembrolizumab.

My gut feeling is that in the adjuvant space for the non-clear cell bucket of histologies, it is really a data-free zone. We tend to rely on surveillance until disease recurrence, hoping that these patients do not have a recurrence. If we are extrapolating from early metastatic and micrometastatic disease data for single-agent pembrolizumab, maybe we can offer it, but it is certainly a bit outside of the label for adjuvant clear cell kidney cancer.

Now, I love to offer trials for our patients in this space. There is one in development in the NCTN out of the Emory group: pembrolizumab versus pembrolizumab with tivozanib. Also, Dr. Toni Choueiri highlighted an mRNA vaccine study today: V940 with pembrolizumab versus pembrolizumab alone.

Dr. Albiges: We need to generate data for non-clear cell in the adjuvant space. One thing we have not touched on is the question of toxicity. Dr. Bari, could you give us your view on whether there is a different toxicity pattern when using an IO/TKI regimen in patients with non-clear cell histologies? Or is it exactly what you are seeing in your clear cell RCC patients?

Dr. Bari: Based on my experience treating these patients, as well as the results of the pembrolizumab/lenvatinib or the nivolumab/cabozantinib trials, the toxicities were almost similar in patients with non-clear cell histology compared to clear cell histology. More than 50% of patients had grade 3/4 toxicity with the combination of IO plus TKI. However, I have not seen differences in toxicity based on clear cell versus non-clear cell. There would be a difference in toxicity in medullary cancer or in collecting duct when treating with cytotoxic chemotherapy, but that is a different treatment altogether.

Dr. Albiges: So, when you are managing your patients, you are essentially doing the same workup and informing them about the risk of toxicity with the IO/TKI regimen ahead of time.