Chandler H. Park, MD: How I envision kidney cancer in the future is, that kidney cancer, if you think about it, is a cancer that starts in the kidney. But everybody diagnosed with kidney cancer has a unique kidney cancer, even though it's called clear cell. The analogy I use to show you the heterogeneity or how variable kidney cancer is this; we all know about COVID-19. COVID-19 is a virus that goes into the air, goes into our lungs, and there are different variants.

So the original variant and the alpha,…the beta, and the delta. Each variant is different from the first one. So, everybody diagnosed with kidney cancer, cancer started in their own body. Based upon the DNA of the kidney there was transformation into a cancer stage. So everybody with kidney cancer, everybody [with] clear cell kidney cancer has a unique variant. So, we need to get better … at [coming up] with a personalized treatment. If 70,000 to 80,000 people get diagnosed with kidney cancer in America, that's 70,000 to 80,000 different variants of kidney cancer.

How do I envision going forward? There are some really good provocative studies where you check the biopsy of the kidney cancer and they do genetic signatures, whether it is DNA of each person’s specific cancer DNA in the kidney cancer or the mRNA. Which is what the messenger RNA is. Which is something that kidney cancer becomes, it becomes a protein. And they're actually checking that to see what would be the best treatment for that specific patient.

For instance, we were talking about some patients that we give immunotherapy [IO], i.e., nivolumab and ipilimumab. For some patients I give lenvatinib and pembrolizumab, others I give cabozantinib and nivolumab, and then for others I give pembrolizumab and malaita, or axitinib. So in the future, what they're doing is this study right now, Dr Brian I. Rini [, MD,] is leading and it's called the OPTOC RCC [NCT05361720]. They're actually checking the mRNA of these person-specific cancers and they're trying to figure out which treatment is best based on that person's unique, clear-cell kidney cancer.

That's where it's going. It's going towards precision treatment, personalized treatment, where instead of having 4 different FDA [the United States Food and Drug Administration]-approved treatments, now we'll know which of those 4, is the best. Based upon that person's unique mRNA signature based on their clear-cell kidney cancer.

The other thing is, and this is very promising,[in] 2019, you know, the Nobel Prize [in Physiology or Medicine] was awarded to, a group of scientists, most notably from Dana-Farber. And what they found is a gene called the Von Hippel-Lindau gene. They found out the pathway that led to clear-cell kidney cancer, so patients tend to have this Von Hippel-Lindau mutation, and if they do, they're at a higher risk of developing kidney cancer. By going through this pathway, they found that the mechanism or the path is kind of blocked by an area called the HIF-2 alpha transcription factor.

So we have medications that are in clinical studies right now. They're called HIF-2 alpha transcription factor inhibitors, [such as] busudanulfan. And the studies look very promising. So this treatment is going to go up the line of treatment. In fact, we had this clinical study in many centers as well, where you have pembrolizumab and lenvatinib and we also had this third medication called busudanulfan, this HIF-2 alpha transcription factor. And that's going to be emerging for another treatment for kidney cancer.

The other thing that's moving forward in terms of kidney cancer is going to be the imaging. For instance, we have different types of imaging for cancers. We're very familiar with something called a PET scan. When we do a PET scan, it's called positron emission tomography. They inject a positron-emitting medication called FDG [fludeoxyglucose] into the blood, which binds to areas that are very active, i.e., cancer cells. So we use FTG PET for lung cancer and lymphoma. Recently we have something called PSMA PET. PSMA is also a PET scan. But instead of FTG, they use PSMA and PSMA stands for prosthetic specific membrane antigen, so specific for prostate cancer. So in the future, they're going to have a PET scan specifically for kidney cancer. And there was some emerging data at the ASCO [the American Society of Clinical Oncology yearly meeting] recently here in 2023.

In the future, we will be able to pick up cancer of the kidney much faster. You might ask, well, when do we need that? Our patients, who had kidney cancer, had the cancer removed with radical nephrectomy or total nephrectomy. They take everything out. So we have an FDA medication called pembrolizumab. And pembrolizumab is used for adjuvant treatment. That means after you get the cancer out, you give immunotherapy [IO] for up to 1 year and try to prevent the cancer from coming back. The problem with IO is that some of these patients might already be cured and we might be over treating these patients. In fact, studies have shown up to 10%, 1 out of 10 people that we give IO, can create a permanent side effect, such as a thyroid condition. I've had patients diagnosed with diabetes. I've had patients diagnosed with adrenal insufficiency. So in the future, what's going to happen is they're going to have this PET scan specifically for kidney cancer after they have surgery, and this will be able to pick up cancer to see if they truly need IO after surgery.

Tian Zhang, MD, MHS: I think some of the unmet needs that remain are now that we have effective treatment strategies in advanced or metastatic kidney cancer, how do we optimally sequence these therapies? So we are finding good candidates for each combination and giving patients combinations in a sequence of each treatment is life-extending.

But how can we sequence so that we're finding different treatment resistance mechanisms and also trying to tailor our sequential therapies to conquer those treatment resistance paradigms? Are there other emerging agent treatment strategies? Absolutely. There are many agents, an early clinical investigation includes cellular therapies like CAR T cells [chimeric antigen receptor T cells], as well as novel IO targets like LAG3 [lymphocyte activation gene 3] and TIGIT [T-cell immunoreceptor with immunoglobulin and ITIM domain]. So a lot more to come, I think, for kidney cancer. And then finally, there is a whole HIF-2⍺ agent called busudanulfan, which is right around the corner in terms of its approval for advanced stages of kidney cancer. It's currently approved purely for patients with Von Hippel-Lindau syndrome. We're about to see a very large trial report out showing benefit in the refractory kidney cancer cohorts so I'm excited about that and about where it will bring busudanulfan in other stages of kidney cancer.

Thank you for joining me to learn about advanced kidney cancer. We hope you found this educated patient Sound Bites program to be informative and helpful.

Transcript is AI-generated and edited for clarity and readability.