Educated Patient® Kidney Cancer Summit Panel on Immunotherapy/TKI Combo Treatment: April 9, 2022

This panel was moderated by Kristie L. Kahl and featured Dr. Thomas Hutson, Louise Gunter and Meryl Uranga.

Kahl: Dr. Hutson, my first question is actually for you. Could you offer an overview of IO/TKI combinations and kidney cancer? I know we'll have a presentation on it later. But just to give a little bit of background for this discussion.

Hutson: Yes, sure. So I think so far what we've heard is that we've talked a lot about the surgery, and we've talked about the adjuvant therapy and even from the talk on adjuvant therapy by Dr. Haas, we saw that there is both an oral agent Sutent (sunitinib). But then what we felt we had some limitations within and now we have these immune therapies. And we're always, in medicine, trying to take more active therapies and studying them obviously earlier and earlier in the disease.

We've had modern therapy for kidney cancer now for over 20 years. There was two different generations, if you will, of these modern therapies. There was the original group of predominantly oral therapies like sunitinib, pazopanib, (Nexavar [sorafenib]) and (Inlyta [axitinib]). And then we saw over the past five years, really, this newer wave of therapies that for the most part, have been proven to be more active. And they include some of the newer generation oral therapies, such as (Cabometyx [cabozantinib] and (Lenvima [lenvatinib]), as well as a whole class of drugs called immune therapies or checkpoint inhibitors. And (Dr. Rana) McKay mentioned that a Nobel Prize was won for that discovery in 2019, by Jim Allison at MD Anderson.

And so we now have shown that we have these immune therapies that show benefit as initial management of patients with metastatic disease, we have newer oral therapies. And naturally, since they work differently, we know that we want to inhibit the VHL abnormalities and the angiogenesis that that brings. But now we have this role of stimulating the immune system and overcoming the immune resistance. Is there a way to combine these agents together, and that has been the history of cancer care from the beginning when we use in other cancers, we use chemotherapy cocktails, if you will. And it's always been a belief that more than that, it's going to be unlikely that just one single drug is going to be enough to kill a cancer, that it's probably going to be take multiple drugs in a cocktail or regimen. And certainly, that's what we've seen in other tumor types. So it's natural for us to want to combine.

And so there's more to this story than just that it's not only do we have these very active drugs, we want to combine together, we want to do some with some type of scientific rationale. And we found that not all of the therapies that we have for kidney cancer are combinable. And it's only a couple different ones, the ones that you're going to hear about today that have actually shown to be safe, that's the most important. They've got to be tolerable, there can't be too much side effect. And they've got to have high levels of activity with the combination of two drugs is better than the single drug itself. And so we have shown that some of the oral drugs that work against the VHL and the angiogenesis, actually work on the immune system in a positive way, that they help augment the immune system and so that when we use an immune therapy, like one of the checkpoint inhibitors, the Keytrudas (pembrolizumab) and the Opdivos (nivolumab), those therapies, when we combine the two there can actually be synergy.

And so the proof of that theory from the lab is in these large randomized trials that we're going to go through. So we generate a theory of why two drugs should be put together. And then we test that theory and these clinical trials to show what we thought was going to happen and that it's safe and effective. And so we're using these, you're getting two different mechanisms of action for maybe a one-two punch. And we ultimately want to have synergy, which means one plus one equals three. And so that's what we're looking for. And so hopefully that will wet your appetite for the discussion that's going to happen here of these combinations of IO/TKI moving forward for the afternoon sessions.

Kahl: Absolutely. Thank you for that. And Meryl, my next question is for you. Can you discuss your journey with kidney cancer and in particular your treatment options over the years?

Uranga: Thanks Kristie. Happy to be here. Happy to share my story today. I was diagnosed incidentally with stage 4 kidney cancer in April 2017. I am days away from that five-year milestone here. I was seen in the ER for acute appendicitis. And that was done for the pain that I was having with the appendicitis, which uncovered a roughly nine-centimeter tumor on my left kidney. It was pretty jarring because I was in pain and having appendicitis and I had to have an emergency appendectomy and at the same time I'm being hit with a possibly metastatic cancer diagnosis. I say that because they noticed in the CT something in my right lung as well.

So I needed to just deal with the immediate emergency issue that I had. But while I was in the hospital recovering from the appendectomy, I was visited by urologists. And so that whole whirlwind began. Looking back, it was very confusing, almost like some things I don't even really remember that much. But I recovered quickly from the surgery and was thrown directly into oncology, surgery, etc. I really didn't know much. I wasn't really in a real, like educated situation, an informed situation. I was just kind of going through the motions.

You know, I did a little bit of cursory research to make sure that you know, I was seeing the right type of people or whatever, but it was much later that I went on and became more involved and empowered with my care. Anyway, of roughly a month, almost to the day after my appendectomy, I had a full radical nephrectomy. That was a rough surgery, I recovered from it and immediately went into surgery for lobectomy, well, first, I had a bronchoscopy that confirmed that it was RCC in my lungs. And once that was confirmed, I was able to heal relatively long enough from the nephrectomy to then have a lobectomy. Before the lobectomy, the thoracic surgeon insisted on a MRI of the brain, at which time there was a lesion discovered in the the corpus callosum, where that initial one was. And so I had to have a treatment or Gamma Knife treatment added to the regimen that I was facing. So this is all happening between like April and July of 2017.

The oncologist that I was seeing, he came very well recommended, but he was a general oncologist in a community hospital setting. The urology team I was working with recommended him. He was, you know, well known in the community, well respected and I didn't know better at the time that I really needed to reach out to a more specialized team. But I did go through each treatment and I was generally told that I would be free of disease with these local treatments. And I was after the two surgeries and the gamma knife, I was considered NED, no evidence of disease, and I stayed that way for roughly 18 months. I was on active surveillance, I was getting scanned and, you know, kept up with watching what was going on.

During that time, I kind of delved into the support world, educating myself way more and learned that I really needed to move into a more specialized area, especially for the time if and when I would be using systemic treatment, which that's what I'm going to focus on here. And that happened within those 18 months.

I moved my care to our local university setting Emory. My oncologist is a specialist in the area of genitourinary cancers, typically kidney. I felt very comfortable immediately in that setting. And those 18 months had passed and it was time to work on systemic treatment. I had a very good team in place I trusted. I didn get a second opinion from UT Southwestern, but I went with my initial treatment once I had seen they had seen some progression with the (Yervoy [ipilimumab])/nivolumab combination, which is the double immunotherapy. And that was in late 2018. I got through three infusions of the Yervoy and I developed a high-level adverse event called hypobursitis, which was basically an attack of the pituitary gland. I had very bad headaches and just had no idea what was going on. It turned out that my pituitary gland had been compromised, wasn't producing the signals to create cortisol. So, I had adrenal insufficiency, which is a permanent condition that I'm still managing. But I continued on once I treated that with high-level steroids. I felt better immediately. And I was able to resume treatment on the monotherapy, which was the Opdvo. And I did that for quite a while until 2019.

And, generally speaking, with the double immunotherapy, I did not get a huge response from it. I don't know if it was even technically considered a partial response. But it did kind of, I guess, for lack of a better term kind of dumbed down the cancer. It got very stable. There was a little bit, in 2019, in the summer, while on the Opdivo monotherapy, there was some progression. So that was when we switched to the double immunotherapy and TKI, which is our topic today. So sorry, took me a long time to get there. But that's my story.

Kahl: Alright. So, Meryl had just mentioned that she had a team that she had trusted. So, Dr. Hutson, going off that, why is it important for patients to talk with their health care teams about their treatment options, like an IO/TKI combination?

Hutson: Yeah, I mean, I think you need to be comfortable with your care team. And to be honest, you need to be searching out. And you have the potential as a patient and a caregiver to be more informed than any generation before you. And it's because of the internet. There's a variety of new support groups and things that can help steer you the right way. It can be overwhelming at first. And sometimes, you know, the last thing you want to do is sit there and try to figure out, are you with the right care team?

But ultimately, someone, you or your family members, needs to, when the dust settles, figure out, am I getting the therapy, which is considered the current standard of care? if I'm not, having the discussion, you know, in a way because your physician may have a perfectly good reason. But it's understanding, you know why that is and what the rationale for therapy is. You'll hear today that at least in 2022, virtually all should get some type of an immunotherapy backbone, whether it be IO/IO, as in your case, or whether it be an IO/TKI, and that should be the way it is. And if that is not going to happen in the first time. Second, there needs to be a rationale for that, that makes sense. If that's not happening, then you need to seek that out. Kidney cancers are a rare enough tumor that a lot of general oncologists may not have a lot of experience with it, compared to a Center of Excellence.

Raw transcriptions have been lightly edited for clarity.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.