Unmet Needs and Future Perspectives in Advanced RCC


The panel concludes with final thoughts on unmet needs and future perspectives for the treatment of advanced clear-cell RCC.

Tian Zhang, MD: When I’m thinking about cabozantinib in combination, we’ve seen some great data from cabozantinib with atezolizumab. That forms the basis for the ongoing CONTACT-03 trial of cabozantinib vs cabozantinib and atezolizumab. We also have promising combinations of tivozanib and nivolumab. A couple of tivozanib-nivolumab trials are ongoing. The TiNivo-2 trial is in progress. There was a poster at ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium]. Finally, belzutifan with cabozantinib, which we highlighted earlier, is certainly very promising as well.

Thank you all for so much for this superhelpful, insightful, rich, and informative discussion. Before we conclude, I’d like to get some final thoughts on unmet needs and future perspectives on advanced renal cell carcinoma [RCC] from each of you. Dr Ornstein, can you start us off?

Moshe C. Ornstein, MD, MA: On the 1 hand, we’ve come a long way in treatment-naïve clear cell RCC. Any option we discussed is appropriate for treatment, and toxicity management is critical. One of the primary unmet needs from my perspective is the management of patients with non–clear cell renal cell carcinoma. We’re extrapolating a lot of the clear cell data into the non–clear cell setting. Of course, we have the PET-MET trial, the PET-MET2, and some of the biomarker-driven studies as well. But it’s still largely an area of unmet need.

Lastly, I’d like to emphasize duration of therapy. We’re giving patients a lot of medications up front. We’re giving them at least doublets, likely triplets, and possibly even more. I’d love to continue the work and some work you’re doing as well—de-intensification of therapy, intermittent therapy, early discontinuation of therapy—so that we’re giving patients the best chance to succeed in the long run but minimizing toxicity by taking them off therapy, or at least de-intensifying it relatively early on in the treatment course.

Tian Zhang, MD: Just to chime along with that, the treatment-free survival intervals we’re starting to see from the CheckMate 214 trial are helpful and clinically relevant for our patient population. Thanks for highlighting that, Moshe. Dr Braun, your closing thoughts on unmet needs and future perspectives?

David Braun, MD, PhD: First, it’s worth taking a step back and acknowledging that we’ve had tremendous improvement in change in the management of advanced kidney cancer over the past 10 years. Survival was really poor, but now we’re to the point where more patients are getting long-term durable survival. Maybe it’s controversial. I’d argue that a fraction of patients are truly cured of their metastatic disease. They really use a cure fraction. But that number is far too small. The unmet needs, in my mind, revolve around that. How can we take something from a proof of concept—that a cure fraction, a treatment-free survival, is possible—and realize that vision for more patients? That’s going to require careful clinical studies but also translational studies and scientific investigation, to understand mechanisms of response and resistance and combine things in a rational way.

Lastly, as Dr Ornstein was mentioning, the focus of almost this entire conversation has been on clear cell RCC. But up to a quarter of patients with RCC will have varying histologies. So far, the paradigm has been to extrapolate from clear cell to non–clear cell, but they are distinct diseases with unique biologies. Diving into understanding the biology of those individual tumors so we can rationally direct therapies is going to be really important.

Tian Zhang, MD: I can’t agree more. Teasing apart each of the non–clear cells in its own histology and tumor biology will be super-important for us to move the needle. Thanks for that, David. Dr Bilen, what are your closing thoughts on unmet needs and future perspectives?

Mehmet A. Bilen, MD: First, I’ll thank all the panelists. It was a wonderful discussion. I’m glad to be part of this wonderful family. The future is bright. There are a lot of smart people working on kidney cancer, and hopefully 1 day we’ll be able to cure this deadly disease. In terms of the future perspective, we highlighted biomarker efforts. Hopefully in the near future, we’ll have an easy biomarker that can guide us and our patients.

The second important thing is novel agents and novel pathways. HIF inhibitors are going to be near the finish line, but we also want to see other pathways in other drugs. There are a couple on the near horizon, such as BiTEs [bispecific T-cell engagers] and CAR [chimeric antigen receptor] T cells. Hopefully, with all these novel treatment options, we’ll be able to offer very effective treatment to our patients.

Tian Zhang, MD: Thank you so much. It’s so important for us to have newer targets and more exciting combination strategies, but we also need to think about the balance. There are lots of trials to be done and lots of things to learn. All of us on the call are all trying to learn more about our patients in these ways.

Dr Barata, last but not least, what’s on top of your mind? Your closing thoughts?

Pedro C. Barata, MD, MSc: Great discussion. It’s a pleasure to be here among you. I learned from you guys, as always. Thank you for having me. I fully agree with the great points my colleagues made. I’d like to highlight what we’re seeing in the kidney cancer world, which is fantastic. We’re seeing the emergence of different groups and consortiums—collaborative groups making significant effort and spending a lot of energy in putting out very smart, well-thought-out studies. PDIGREE is a great example. It’s awesome to see it. You can feel it. At ASCO GU, there was an excitement about kidney cancer day there. The future will bring us more collaboration, which is going to bring more thoughtful studies. Because this is kidney cancer, a deadly disease with unmet needs, I’d like to emphasize the importance of considering patients with advanced kidney cancer for the trials available, closer to whatever anyone is practicing. That’s the way to go. It’s easier to do in clear cell than in non–clear cell. It’s just for consideration, but please consider enrolling your patients in the thoughtful trials out there. Ultimately, that will help us cure patients with kidney cancer. Thank you again for this wonderful discussion.

Tian Zhang, MD: That’s an amazing summary. I promise I didn’t plant that answer. Thank you, Pedro, for that plug for all the clinical trials that are ongoing to help us build on standard of care. I would add that we certainly have a wealth of riches for our patients in frontline and subsequent-line therapies. But in the frontline setting, our immunotherapy combinations haven’t been compared head-to-head. We’re coming out of the era where we have Sutent [sunitinib]–controlled trials, we’re hoping we’ll see more trials building on immunotherapy backbones. We certainly need to select the right patients for optimal treatments. As my colleagues have highlighted, these biomarker approaches are going to be key. Much work is still needed for these types of treatment selections.

Thank you to all the members on our panel. I always enjoy speaking with you and collaborating together for the good of our patients. To our viewing audience, thank you for joining us. We hope you found this OncLive® Peer Exchange® discussion to be useful and valuable to the treatment of your patients.

This transcript has been edited for clarity.

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