Evolving Practice Patterns for Advanced Clear Cell Renal Cell Carcinoma - Episode 10

Final Thoughts on the Management of mRCC

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Bernard Escudier, MD: I’m still waiting for the third mechanism of action. We have VEGF. We have PD-1. I don’t think we have found the third one, which is going to completely change the metastatic kidney cancer field. I’m hoping we’ll find it and we’ll have the Nobel Prize again.

Toni Choueiri, MD: No MTOR inhibition?

Bernard Escudier, MD: No.

Toni Choueiri, MD: No HIF2 inhibition?

Bernard Escudier, MD: No, it’s not new.

Toni Choueiri, MD: OK. Dr McKay?

Rana McKay, MD: We’ve made great advancements in the field. There are patients living longer and better, but we’re not there. We need to have smartly designed trials, an integration of biomarkers into the trials that we’re designing. How do we make sure the right patient is getting the right combination, limiting their toxicity, and maximizing efficacy? Excited to see that evolve in the years to come. New drugs with new MOA [mechanism of action] absolutely are needed.

Toni Choueiri, MD: Great. Dr Tannir, how is the field going, and what are your final thoughts?

Nizar Tannir, MD, FACP: For the next 2, 3 years we’re going to still be I/O–I/O [immuno-oncology]—as I said at the outset—vs the I/O-TKI [tyrosine kinase inhibitor] camp. We’re going to see data from CLEAR, which probably are going to be better than from CheckMate 9ER and KEYNOTE-426. I do agree with Bernard that the way they dosed pembrolizumab-lenvatinib in the CLEAR study is toxic. I don’t think people tolerate 20 mg daily of lenvatinib. We talk about biomarkers all the time. For decades we’ve been talking about biomarkers. This is what I believe should be the focus of funding from the NIH [National Institutes of Health], and maybe European agencies. Industries should focus on biomarkers to guide us, to select patients based on prediction of response to these therapies and also prediction of toxicity. Toxicity is an issue here. Management of these AEs [adverse effects] is challenging. Biomarkers can predict that. Who’s going to get myocarditis? Who’s going to get myasthenia gravis? Because these are fatal 50% of the time. If we can predict which patients are going to have these problems, we can avoid that or treat them in a way to avoid those toxicities. I am excited about the future. I differ from Bernard about the CAR [chimeric antigen receptor] T. There are 2 companies that have CAR T-cell therapy in clear-cell RCC [renal cell carcinoma] targeting CD70. There’s a company in Massachusetts you know about it: CRISPR [Therapeutics]. There’s a trial that is ongoing already with the CRISPR CD70 protein. And there’s another company, Allogene [Therapeutics], which also launching a trial in lymphoma and in clear-cell RCC. There is the possibility that in the future we will use CAR NK [natural killer] cellular therapy, which is less toxic. Perhaps it will circumvent, and we’ll avoid the toxicity of CAR T cells. I’m excited about the HIF. I’m excited about the glutaminase. We’ll see if we can add some triplet in the next 3 to 5 years. We’re going to have to build on the achievements of yesterday and build with triplets on the backbones of the doublets we have achieved.

Toni Choueiri, MD: OK. Finally, Dr Voss.

Martin Voss, MD: Everyone is so excited. There’s little excitement left for me here. I do have to concur that it’s wonderful to see how far the field has come in just a few years. The thing to take away here—I’ve said this before, and I’ll say it again—is that I don’t think we’ve reached the ceiling. Pushing the envelope so far has worked, and we have all been excited about the efficacy we’ve seen. With CheckMate 9ER as an example, we have been surprised by how manageable these things are for the majority of patients, as we’ve learned as a field. We should build on that and not dial it back. If I have 1 wish for drug development in the field moving forward, I wish we’d have fewer studies in which we just throw everyone on and then stare at CR [complete response] rates and subgroup analyses that are too small for us to interpret. [Instead, we should] have studies that are more geared to subgroups of patients from the get-go with statistical designs that actually build to answer these questions in meaningful ways. It’s hard to see through all the different regimens that we have on the market. For those who don’t use kidney cancer drugs every day and for all of us who do, it’s sometimes hard to see across all the different pathways that are in development. But I do think that the latter is wonderful, and all of us can go and run with the various CAR T cells, HIF2 inhibitors, glutaminase inhibitors, and cytokines. I’m sure that more exciting things will come for our patients, which is what matters.

Toni Choueiri, MD: That’s great. It was my pleasure to have this wonderful panel. I know each of you very well. This was a rich, informative discussion. Thank you again. Thank you to our audience. I hope you found this OncLive® Peer Exchange® discussion to be useful and informative.

Transcript Edited for Clarity