Patient's Perspective on Pembrolizumab/Lenvatinib Use in RCC

Thomas Hutson, DO, PharmD, and Cesar Fuentes discuss the diagnosis of renal cell carcinoma.

In 2009, Cesar Fuentes was first diagnosed with renal cell carcinoma (RCC). He had the tumor resected, but in 2022, he had a recurrence and was referred to Thomas Hutson, DO, PharmD, director of the Genitourinary Oncology Program at Texas Oncology and codirector of the Urologic Cancer Research and Treatment Center at Baylor University Medical Center in Dallas, Texas. Here, new treatment options and strategies were employed to get Fuentes into remission again.

During an Around the Practice®program, Hutson spoke with Fuentes regarding his diagnosis, his treatment regimens, and any adverse effects (AEs) he experienced during therapy. Additionally, Fuentes provided some advice for patients and clinicians regarding how to best approach this disease.

Initial Diagnosis and Determination of Treatment

Hutson: Could you tell us the story of your diagnosis of RCC?

Fuentes: The first time I had RCC was in 2009. The way it was discovered was because I saw blood in my urine. I had kidney stones many years before that, so I thought it was a recurrence of that. I went to the hospital, and they found nothing. Later that same day, I became sick with nausea and [had] more blood in my urine. I called an ambulance to take me to the hospital. Then I had a scan, and that was the way the tumor was found. This was 2009; it was stage I [disease]. I chose to have only the tumor resected, or a partial nephrectomy, as opposed to having an entire kidney taken out because I was afraid that I would end up on dialysis someday.

[In the past] year, I saw this huge bump growing on the left side of my neck. It had grown so much that it was displacing my Adam’s apple. At that point, it was obvious there was something wrong, so I began treatment. I went to Lance Oxford, MD, who was an ear, nose, and throat specialist at Baylor University Medical Center. Ultimately, [the bump was] resected, and the tumor was about 9 cm. It was a huge tumor, but the cancer was not just in the thyroid area. It was also in the lymph nodes and around my chest. There’s a bit of cancer in my lower left jaw too. It was Oxford who referred me to Hutson, and I was very pleased to find out that there are some good medicines for kidney cancer, mainly pembrolizumab [Keytruda] and lenvatinib [Lenvima]. They have worked very well, and [I had] some stunning tumor shrinkage. I will be on lenvatinib maybe for the rest of my life, but I’m very lucky and fortunate that there is adjuvant therapy, because in 2009, there was nothing that was effective.

The AEs have been overall mild and manageable enough. For example, after I am [done with my] infusions, I’ll be able to immediately go to a spin class or a cycling class. Later in the day, I may be a little more tired, but it’s very manageable. In terms of the lenvatinib, I take a pill every night. That one causes a few more AEs, especially in the tongue and with eating, but they are manageable given the benefits.

Hutson: When you were first diagnosed, did you ever feel despair? Have you always been so positive? How does that positivity [affect] your tolerability?

Fuentes: When I found out that I had cancer in 2009, I was terrified. The reason was [that] I didn’t know what cancer was. All I knew was about the fast rate at which cells divide, which was semimeaningless to me. I decided to do a deep dive into biology to get an understanding of what cancer is. I even took a course in biology at Duke [University in Durham, North Carolina,] for sophomores who are [premedical majors]. From there, I branched out into deeper things about cancer. For a civilian, for a nonspecialist, I have a passable understanding of what cancer is.

Once I had a parameter of what was going on, I was much calmer. My oncologist at that time had said there was a chance the cancer would come back in about 10 to 12 years. It was almost like clockwork. I had gotten my primary care physician to allow me to receive scans every 2 years, but I made a costly mistake. [Because] it was kidney cancer, I thought it would come back in the kidneys, but it didn’t. The second time, it completely bypassed the kidneys and went directly to my lymph nodes and elsewhere. That’s how it got to be such a late stage.

The second time it came back, I was terrified for about 3 days. Having been through this before, I knew that I had to start moving immediately and get all the [pieces] in place. I’d also taken care of my parents when they were very sick and had long, hard deaths. I was familiar with the medical establishments and bureaucracies that I had to navigate. Once I started getting all my [pieces] in line, it was very calming and soothing because there was a pathway. It was especially good when I found out that there were these 2 therapies, lenvatinib and pembrolizumab, that could be used. A lot of the reason my mindset is positive is because I still lead a normal life. It hasn’t impaired me to a huge degree. There are the eating issues, which are manageable. My feet sometimes hurt, but given that I have stage IV cancer, I think those are minor overall AEs.

Available Treatment Options for Recurrent RCC

Hutson: Until recently, there was no proven therapy that could be taken after surgery to reliably reduce the risk of recurrence. That changed 2 years ago with the phase 3 MK-3475-564/​KEYNOTE-564 trial [NCT03142334], which led to the approval of pembrolizumab, one of the therapies Cesar is taking to manage his cancer.¹ Given for
1 year, pembrolizumab has been shown to reduce the risk of recurrence by 30%. At the [2023 European Society for Medical Oncology Congress in October], we saw overall survival [OS] data reported with an HR of 0.69.² We’re looking forward to scrutinizing those data more closely, so we do have OS impact as well as recurrence-free survival from 1 year of adjuvant therapy.

Often, even in our patients who [have the] highest risk of kidney cancer, we will scan them quite vigorously the first 5 years because, statistically, that’s when most of the cancer recurs. Beyond 5 years, the likelihood of routine imaging picking things up is much less. Even if you [had aggressive scans done], you may have been in the same place you are right now.

[When I have a new patient], we spend a lot of time on the first visit. It’s usually the longest visit,a good 30 to 45 minutes. We talk through a lot of the information I’ve already provided. I want to educate my patients. I see patients of all types. Some are completely unaware of their cancer or anything about it. Others have done extensive research and sought me out to treat them, and they’re well versed. I want to make sure that the playing field is level.

We go through a lot of the information that I’ve provided about the background of cancer, and then we specifically talk about the management and advances we’ve made to get where we are today and the role of immunotherapy and oral therapy, or combination therapy, as being a standard of care.

Most patients who receive these therapies can expect to have a benefit. The benefit can be at least stable disease. A large portion of patients will have tumor shrinkage. There’s even a small rate of complete responses with these therapies. However, these therapies often require lifelong administration, and there is a chance that, over time, resistance
can develop.

When I’m first seeing a patient, I want to make sure before we start the therapy that we have a fresh set of imaging studies. We want to look right before we start therapy and have a good idea of where the cancer is. We’re going to compare [with] that at preplanned intervals. Usually, it’s a 3-month interval, which, in the case of the 3-week cycle of pembrolizumab and lenvatinib, would be 4 treatment cycles. We will repeat scans, and we want to show that there is a benefit.

For us to say there’s been a win for the therapy, there are 3 things that need to happen. One is important and trumps everything else: the patient’s perspective. My goal in this setting is to make sure that the patients are living life and functioning to the best of their ability. Sometimes I have patients who are willing to [experience] excessive AEs. I have to walk them back a bit and try to remind them that being in bed all day is not the goal of our therapy. The goal is what Cesar presents with, which is trying to live as normal a life as possible. We want to adjust the therapy to get to that point. That’s the most important thing: Are we accomplishing the patient’s goal?

The second, from a medical standpoint, [is the following question]: Is it working on imaging studies? Are we seeing at least stable disease? Are we able to control the cancer? The third thing comes down to the toxicity and laboratory studies that the [physician] has to monitor. Is it safe from a medical standpoint for us to continue?

Those are the 3 factors that we want to assess every time we evaluate whether or not the cancer is responding to therapy. It’s also important to make sure before we start therapy that the diagnosis has been confirmed. Obviously, in the case of Cesar, with his recurrence being a later recurrence, we did have pathology. Oxford provided the pathology and confirmed that this was kidney cancer. Especially in situations [such as] the way Cesar presented, where there has been a long interval, there could be another cancerous process. Just because someone has a history of kidney cancer, we can’t assume that, later in life when something else develops, it’s kidney cancer. You want to make sure that you perform a biopsy and prove the type of cancer because the therapies for cancer are so different. Sometimes, we don’t have to biopsy because the clinical course is so close together to the diagnosis that it makes clinical sense, and we have a high probability that it is indeed cancer.

Cesar, you were inclined to take a course to understand the disease a little. Were there any other resources that were useful to you? Was there any other group, such as the Kidney Cancer Association that you were involved with, or did you use any other resources?

Fuentes: There were a lot of resources offered to me, but reading about a disease, in retrospect, turned out to be my therapy. It was very calming; the more I understood, the calmer I became because I had certain boundaries of expectations. Cancer is an endlessly fascinating disease, but it’s also a ghastly disease. I know when I go and have my infusions, I see a variety of people. There are some who look weak and frail, and there are others who look like they [came from] playing a rugby game. Things like that give me hope. I did go to a meeting once at Cancer Support Community North Texas, and that was helpful. At this point, though, it’s such a part of me. I don’t like having cancer, but it’s a part of me. I don’t feel the emotional weight yet. At some point, that may happen, but it’s not here yet.

Adverse Effect Management

Hutson: When we first met, were there any questions that you thought were important to ask, or [are there questions] that would be important for others to ask when they’re initially meeting with their oncologist to decide on a regimen?

Fuentes: One of the important things to consider is the potential AEs from treatment. It’s crucial to have an idea of what to expect physically [because] cancer treatments can have varied effects on different individuals. Cancers can be as individual as a fingerprint, and how people react to treatments varies. It’s important to get a spectrum of possibilities of what you can experience. For me, the critical test was that first scan after I met you. It’s critical because you begin to get direction on how things are going. I remember that, after that first scan, there was significant tumor shrinkage. In fact, I took an Excel spreadsheet and started figuring out percentages. It was stunning. There were tumors that had shrunk up to 50%, others that remained stable, and others that had gone down 10%. As a patient, you need to understand what may happen to you physically because that will determine your needs. Will you be able to live by yourself? Will you not? From there on, the test is what those medicines are doing for you and how they are working.

Hutson: How did you manage AEs?

Fuentes: I attempted to delay taking the medication, but I knew I had to start eventually. I’m on [lenvatinib] 20 mg every day, but I get to skip it 1 day a week. This effectively brings me down to 17 mg, which is still above the 14-mg standard dose. Regarding the AEs for pembrolizumab, in my experience, there are almost none. It can be difficult to distinguish between the AEs of lenvatinib and pembrolizumab.

Next Thursday, I will have another infusion, and I may feel a little tired for 7 to 8 hours afterward and maybe the next day, but that’s about it. To get to the point where you have a drug that is as effective as [pembrolizumab] for cancer signifies an incredible amount of medical engineering that has gone into discovering that solution. In terms of lenvatinib, the main AEs have been problems with my tongue and tongue sores, but they’re microscopic; I can’t see them, but they’re there. I have sensitivity to salt and several other types of food. I get these little sores that look like corn [on] the bottom of my feet, but you can take care of those and minimize them by using creams.

The other issue that I’ve had is [that] sometimes I have soft stools. For example, I skip the lenvatinib tonight. By tomorrow night, there will be no problem. On Sundays, I’m very good, and on Mondays, I’m very good. Tuesdays are wonderful. By Wednesday, things start to get a little dicey. By Thursday, things are a lot dicier. Today, they’re even more dicey. I’m still talking to you, so I’m not [bedridden]. That’s the way I’ve learned to manage it. I’m stunned, though, especially after seeing my mother with cancer several years ago, a very different type of cancer, and the issues she had. I was expecting something like that, yet at this point, they have not occurred.

Final Thoughts

Hutson: What advice would you share with patients or [physicians about] treatment? What would be your final words of wisdom?

Fuentes: If you receive a cancer diagnosis, feel free to panic but don’t panic too much. The world is very different than it was a few years ago. Panic enough so that you do something about it instead of simply thinking that it’s the end of your life. It’s not. It’s a very different world. I know that because my mother had cancer and I’ve known other people with cancer. It’s a very different world now than it was even 5 years ago. The medicines I’m on did not exist and were not indicated for my situation 3 or4 years ago, but here they are. Panic enough to do something, but don’t be terrified. You’re going to be terrified; you’re going to be fearful. But don’t minimize it, and just do something about it.

Hutson: Would you tell the [physicians] to listen to their patients?

Fuentes: Yes, [physicians] need to be aware of the patient’s limitations. You also remember that, quite often, a lot of patients can goto you and they’re going to be terrified. [Physicians] are going to have to learn how to deal with patients’ fears and minimize their fears. Given the ages that cancer pops up in patients, generally in their 60s, they are going to have a very different picture of the state of cancer treatment now [compared with] what it was a few years ago. That needs to be dispelled. The treatment landscape is very different. It’s a very different world now.

References

1. Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembrolizumab for renal cell carcinoma across UCLA integrated staging system risk groups and disease stage: subgroup analyses from the KEYNOTE-564 study. Abstract presented at: 2023 Kidney Cancer Research Summit; July 13-14, 2023; Boston, MA. Abstract 69.
2. KEYTRUDA (pembrolizumab) significantly improved overall survival (OS) versus placebo as adjuvant therapy for certain patients with renal cell carcinoma (RCC) following nephrectomy. News release. Merck. November 1, 2023. Accessed November 21, 2023. https://tinyurl.com/4p6nraus