Beckermann on Recent Data and Hopes for the Evolving RCC Landscape

Kathryn Beckermann, MD, PhD

The prognosis of patients with metastatic renal cell carcinoma (RCC) has improved over the years with the addition of immune checkpoint inhibitors (ICIs), and a greater understanding of the RCC tumor biology.

However, it is not uncommon for patients to have resistance to checkpoint inhibition. As a result, experts are constantly looking to develop new treatment regimens and options for patients.

Some of these combinations include using 2 ICIs or an ICI added to a different class of therapy. Combination regimens being evaluated in trials have already led to some encouraging results in the RCC space.

It is important to note that while promising findings have been observed with these combinations, by adding a second agent, the risk of developing an adverse event is increased. Thus, the search to find a biomarker that predicts response to ICIs in the metastatic RCC space remains ongoing.

Additional questions that need to be answered include understanding the tumor microenvironment and how what is in it may affect one's prognosis, delving into the idea of gene expression to understand the biology for individual patients, and more.

Experts are hopeful for the future for patients with RCC, especially due to recent data, some of which were presented at the 2022 International Kidney Cancer Symposium (IKCS 2022).

In an interview with Targeted Oncology^TM, Kathryn Beckermann, MD, PhD, an oncologist at Vanderbilt University Medical Center in Nashville, Tennessee, discussed her talk from IKCS 2022 on risk stratifications and considerations for improving outcomes for patients with RCC.

Targeted Oncology: Can you just give an overview on what you discussed at IKCS 2022 regarding risk stratification?

Beckermann: I think Daniel YC Heng, MD, and Ari Hakimi, MD, both gave wonderful presentations summarizing our clinical use of risk stratification for patients who are first diagnosed and getting standard-of-care therapy, as well as the use of its roles in clinical trial development. Both gave excellent summaries of how the data initially started within the era of cytokine therapy and targeted therapy. Then, both groups have subsequently really tried to continue to strive to improve these prognostic criteria. I would say the highlights that I gained from that was continuing to consider clinical factors, tumor microenvironment factors, genomic characterization, and as we continue to move this field of science forward, we're hoping that this will also improve our ability to prognosticate for kidney cancer.

What do some of the current guidelines say about this topic?

I most easily refer to the NCCN [National Comprehensive Cancer Network] guidelines. Again, this gets back to the fact that in our prognostication criteria, these are used as stratification on our clinical trials. After CheckMate-214 [NCT02231749] showed improvement in the intermediate- and poor-risk disease patients, subsequently, guidelines have recommended use of these treatments approved by the FDA based on their prognostic criteria.

What are some key takeaways from presentations given at IKCS 2022?

While we already have these wonderful clinical and laboratory features that help individualize each patient sitting in front of a physician to inform with the biology of their diseases, I think that many teams are making great strides towards improving that, again, depending on various elements. [This includes] things like, what does the patient bring with them that might make them more likely to respond to treatment? What's within the tumor microenvironment that might change their prognosis? Then lastly, can we understand gene expression and genomic, whole exome sequencing, and add all these variables together to choose treatments and understand the biology for an individual patient, rather than broadly making generalized statements about larger groups?

What current data interests you in the RCC space?

I've seen a lot of exciting data. I learned a lot from the work of Elizabeth Henske, MD, on tying together some of these rare, genetically-inherited syndromes that we think of as being rare. But, if you get down to the biology of it, her group has shown a link between lysosomal biology and genetic mutations.

Another talk looking at cytoreductive nephrectomy in the setting of cabozantinib [Cabometyx] plus nivolumab [Opdivo] and understanding if that's beneficial is a large question that remains. We have a lot of data from the cytokine interferon era, we have data from CARMENA [NCT00930033] and SURTIME [NCT01099423]. I think it was great to hear their efforts in a trial in progress presentation to understand if the checkpoint inhibitor era tand cytoreductive nephrectomy might be helpful.

REFERENCE:

Motzer RJ, Jonasch E, Boyle S, et al. NCCN Guidelines Insights: Kidney Cancer, Version 1.2021. J Natl Compr Canc Netw. 2020;18(9):1160-1170. doi:10.6004/jnccn.2020.0043