Kidney Cancer Questions Answered, From Protein Intake to Clinical Trials

From treatment decisions to protein intake, there are plenty of factors for patients with kidney cancer to weigh. Dr. Thomas Hutson, chief of the Hematology-Oncology Division in the Department of Internal Medicine at the Texas Tech University Health Sciences Center School of Medicine and a member of the CURE®advisory board, recently sat down to answer common questions regarding kidney cancer submitted by readers and attendees of the CURE Educated Patient® Kidney Cancer Summit.

After two years with a complete response, how does one decide to continue or stop Keytruda (pembrolizumab) and Inlyta (axitinib) treatment?

Hutson: There is no answer there. The one simple answer is that the clinical trials of Keytruda had an arbitrary stop at two years that was chosen, not based on necessarily any science. It was just what was incorporated into the clinical trials. If you look at their label, in particular cancer types, they may talk about a two-year stop, and that's generally been what's been utilized.

We do know that there have been some publications in some cancer types that keeping the Keytruda going to the two-year point seems to be better than stopping it sooner than two years. But as far as data beyond two years — because of the arbitrary stop dates — stopping of it in the clinical trials, we don't have a lot of data on continuing it past two years.

So usually, what happens in clinical practice is if you are responding to the therapy and don't have a side effect or something, you would stay on your Keytruda to complete two years of therapy, at which point you would be maintained on Inlyta, theoretically, indefinitely. In my practice, and I know many of my colleagues are starting to look at those patients who are now on Inlyta by itself indefinitely, and starting to have conversations with them about potentially stopping the Inlyta at some point and monitoring them off of all therapy. Now my experience is, and there are no large data sets, I can tell you that, yes, there are patients who are able to stay off of Inlyta and be on no long-term therapy with controlled disease. I can't say that that's going to be a permanent finding for them. We can't say they can use the word cure, so these patients are invariably living CT scan to CT scan, monitoring themselves.

Many patients can get many months off of therapy and years off of therapy before anything comes back. There are groups of patients where things have not come back and they stay off of therapy.

It really has to be a conversation with the patient and their family as to what they're willing to accept [regarding] side effects of therapy versus a chance of recurrence. I have patients who feel different ways about it, and some patients will say, “Unless you can guarantee that the cancer is not going to come back, I don't want to take the risk. I'm taking Inlyta. I'm tolerating it well. I don't want to take that risk unless you can guarantee it.”

In that situation, then they stay on it. In other situations, patients may say, “Hey, I'm willing to try, as long as I can go back on the Inlyta if it starts to grow again,” and then we try it. So it's really an individual discussion with the physician, but I think it should be entertained in all patients that have stable disease that's controlled when they get to Inlyta by itself.

Is there a treatment available that has been well tolerated for non-clear cell chromophobe renal cell carcinoma?

Yes. The chromophobe carcinoma type lands itself within the designation of non-clear cell. There are, if you look in the non-clear cell guidelines that are published by the NCCN, and there are similar groups around the country, most of them are now listing a combination of two different therapies. They use an IO-TKI. They use Lenvima [lenvatinib]. Keytruda is an alternative in first-line, as well as CaboNivo [Cabometyx (cabozantinib) and Opdivo (nivolumab)] are alternatives for non-clear cell.

When you really dive into the data on some of the phase 2 trials that were done that included the chromophobe population, there's benefit from Lenvima and Keytruda. There's benefit from CaboNivo. There's benefit of the combination of Lenvima and [Afinitor (everolimus)]. That's an oral combination that's approved for refractory kidney cancer. We've reported, and I was the first author on a phase 2 trial that looked at specifically Lenvima and [Afinitor] in non-clear cell, and we had a significant component of chromophobe and we found that the highest response rate was in the chromophobe cancer, and that supports the use of Lenvima and [Afinitor] as a therapy.

The challenge is the FDA approval of that combination as a second-line therapy. So, we don't have the ability to give it to someone first line. So, if we're following the approval, you could use, for instance, CaboNivo as a first-line option for chromophobe, and then you would have the option of going on Lenvima/Afinitor as a second-line option, and both of those therapies are shown to have benefit. The checkpoint inhibitors have shown benefit at some level in the non-clear cell. So, there's a handful of therapies.

Is there anything that patients can do to help with severe and chronic kidney disease caused by RCC?

For severe fatigue, the first and most important [thing] is to determine whether there's a secondary cause of the fatigue like anemia, like low steroid levels, what we call adrenal insufficiency.

It could be caused by low thyroid levels. It can be caused by low growth hormone levels or pituitary levels of different hormones. ... But a lot of times, there's no clear explanation for the fatigue outside of it either being the cancer or outside of it being the medication. There's nothing that we can find that's reversible, there's just fatigue. In that setting, we talk about various types of sleep hygiene and exercise — people who exercise tend to develop endurance throughout the day. We look at other medications that could be contributing, especially if they're on pain pills or other things. And I do know in some situations, there are physicians who will try to use stimulants if needed to help with patients that are having profound fatigue. But usually, before just throwing someone on Ritalin (methylphenidate) or some type of stimulant, you would want to make sure that there was not a reversible cause of fatigue, like thyroid, adrenal insufficiency or others. So it does require a workup there. So it is generally going to be a multi-visit, long-term management process with the treating physician. And it wouldn't surprise me if the physicians would consult other doctors, like endocrinologists or even palliative care doctors to help with that.

And then chronic kidney disease. The traditional patient with kidney cancer has some underlying renal impairment, either because they've had a nephrectomy [surgical removal of all or part of the kidney] done and so now they have essentially one kidney instead of two kidneys, or they’ve had a kidney mass that is essentially causing one of the kidneys not to function optimally. So at the baseline, there is going to be some degree of underlying renal insufficiency. The vast majority of patients live out their lives perfectly fine with whatever impairment they have. If the impairment is severe, we will sometimes get nephrologists involved. Most patients do not need hemodialysis. It is true that the therapies we use for kidney cancer can impact kidney function, and so we need to be observant of that.

How much protein is safe to eat when you have renal cell carcinoma?

I think if you have an underlying renal impairment that starts becoming more significant, then you may need to reduce your protein intake. But that type of patient would in my practice already be seeing a nephrologist, and it would be the nephrologist that would be reducing the protein intake. So if there are patients that have more severe renal dysfunction, or they find themselves having a lot of loss of proteins in their urine, then the nephrologist will be working with them on a protein diet. Sometimes they ask them to take more protein in, sometimes they ask them to reduce protein intake. The nephrologist, who’s really the expert in that setting, handles that. But in general, I don’t make my patients restrict protein as a common maneuver.

Clinical trials require that patients get to where that trial is located, which can be difficult, both physically and financially for some patients. How can that be addressed?

The entire Society of Clinical Research is attempting to address that now, partly because it's the right thing to do, partly because the FDA is starting to mandate diversity and inclusion in enrollment in clinical trials, trying to make sure that clinical trials are available in rural America and in populations that may otherwise have not participated in clinical trials.

It is true when you look at a published clinical trial, whether it's in the United States or in Europe or the rest of the world, that the vast majority of enrolled [patients] are Caucasian, so it doesn't represent the full population. So even when we do international studies and we're looking at [them] there's always a small group of Asian enrollments, there's a small group from South America. There's a small enrollment from people who are Black, but it's predominantly going to be patients of Caucasian, Northern European descent.

And so, we know that there are differences among people in that sometimes patients handle therapies a little bit differently. We know that there are different side effects that are more frequent in certain populations than others based on the way their bodies handle therapies, and those are related to genomics and genes and how they're transferred down through their family lines. We want to make sure that we include in trials the real-world population of patients that are going to be receiving the therapies, and so there are large groups that are actively trying to enroll patients in rural settings.

So how are we accomplishing this? Well, one, we're trying to change the way clinical trials are done, where allowing patients as they're identified at these cancer centers that are long distances away from an academic center, for them to be able to get the trial open quickly and enroll without having to have that patient drive the distance in. So those are what we call just-in-time trials, or there's a lot of different terminology we use for them, but some of the larger cancer networks, for instance, the Sarah Cannon Research Institute, which I've worked with, or with US Oncology, or some of these larger groups, and I'm sure even the cooperative groups are starting to look at ways that they can get the therapies out to more, smaller cancer centers, and that requires working closely with the regulatory authorities on what would be acceptable for it. So you have to address, what a lot of the concerns that come in a clinical trial is, is oversight, making sure that the physician that's there at that local center is trained well to recognize all the nuances of that experimental therapy. And how do you ensure that? And so those things are being worked [out].

We're still kind of in the infancy stages, but there have been successful trials that have been done now where this just-in-time mechanism where you have them at smaller, more rural cancer centers have been able to open enroll patients on, it's just not widespread yet. There's certainly a cost involved with that, but that's where the movement is going. So for these patients, the hope is in the future that they can get treated closer to home and get the latest and greatest therapy. That's the ideal. We're just not there yet. We're probably a few years away.

This transcript has been edited for clarity and conciseness.

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