Sarah Yenser Wood, RN, MSN, ANP, AOCNP, leads a nursing panel on adverse event management in renal cell carcinoma.
Sarah Yenser Wood, RN, MSN, ANP, AOCNP:
When you think about first-line regimens for advanced or metastatic kidney cancer, what are your experiences and perceptions with the toxicities of each one? What do you see as the pros and cons of each regimen? From your perspective, what have been the greatest impacts of the switch from the single-agent [tyrosine kinase inhibitor] TKI therapies to immune checkpoint inhibitor–based combination therapies on your practice and for your patients?1,2
MICHELLE RAMPERSAD, NP:
I think in the advanced or metastatic setting, we’re going to end up seeing a lot of these agents. About which one to choose, a lot of it depends on your patient, their overall function status, and how extensive the disease is. Say it’s somebody who has bulky disease and a lot of symptoms related to the cancer. You want to start something that’s going to get a response quickly, so you might do dual immune therapy with ipilimumab [Yervoy] and nivolumab [Opdivo] to get a faster response vs an oral agent. But I think at some point you’re going to see most of the drugs anyway as they progress.
DEBRA SOLOM, ANP-BC:
I agree. I think that the immune checkpoint inhibitor [ICI] combinations are giving a much faster response, and once you get through the ipilimumab part of it, they’re much better tolerated. Pembrolizumab [Keytruda] is good with either axitinib [Inlyta] or lenvatinib [Lenvima]. I see a little bit more adverse effects [AEs] with those, but I like the combinations.
ANECITA FADOL, PhD, APRN, FAANP, FAAN:
When we first started renal cancer [treatment with] sunitinib [Sutent], the first TKI given, from the cardiac standpoint the potential complications [included] hypertension, which is not common, but it is in patients with a preexisting hypertensive problem. That’s what we are dealing with from cardio-oncology. [With] sunitinib there is a rare incidence of left ventricular dysfunction secondary to the medication; therefore, we monitor them with a baseline echocardiogram, and then if there are any signs and symptoms of decreased left ventricular dysfunction, we start them on standard heart failure therapy. But the most common treatment used right now is the combination of ipilimumab and nivolumab.
[The] complications that we are monitoring in these patients [include] myocarditis, which has a very low incidence. I think it’s less than 1%. In the literature, you’ll see the average decrease in ejection fraction [EF] is 1.9% across the board in different studies. It is very difficult to detect these complications because patients sometimes have cytokine release syndrome.
In myocarditis, the gold standard for diagnosis is endomyocardial biopsy, which is very difficult, and it’s not done frequently.
Therefore, from the cardiac standpoint, we just monitor them, sometimes with biomarkers, but there’s no specific biomarker to date. There are studies that are going on, but we just monitor for signs and symptoms and look at the EF, and see if we can catch it early and then initiate treatment. However, there is some literature that says that some patients who are getting these combination therapies for a few months have been noted to have accelerated atherosclerosis, so it is still under observation from the cardio-oncology side. I think that’s what I can say about these medications.
Great. Thank you.
KATHY O’CONNOR, DNP:
I don’t know about you, but I think we’re seeing that there’s a much younger presentation of kidney cancer. I feel like nowadays we have a lot of 30-, 40-, and 50-year-old patients, and, thankfully, most of them are robust and have fewer comorbidities. So, how we’re going to proceed with treatment really depends on age and overall health status. Older people tend to start on single-agent treatment unless they’re a robust person, but [with] the younger population we’re doing combination therapy. Immunotherapy seems to be tolerated fairly well by most of them. Pembrolizumab is tolerated well. We’ve had some issues with ipilimumab and nivolumab but, overall, for the young people, you just plug [along] and keep going.
ERIN PIERCE, NP, MSN, BSN:
I agree. I work primarily with genitourinary patients, so I’m very proficient in prescribing these medications along with the collaborating physician as well as managing the AEs. I agree with [O’Connor] that it really depends on the patient who’s coming in the door, what they’re going to present with, and how we’re going to treat. Is this somebody who we need to be more aggressive with? Are they in extreme pain and really need a quick response? Is it somebody who’s elderly who can tolerate treatment, or what are their possible comorbidities that I need to be worried about? I personally like the combinations. I think they work very well. I think I get good responses with them.
I think the biggest thing that people have issues with—as I’m sure you all can relate to—is trying to figure out which [treatment] is causing the issue.
WOOD: What are the symptoms of immune-related adverse effects [irAEs] that you’ve encountered? What is the most common irAE that you’ve seen in your practice?
We see the pulmonary problemsbecause they’re just so much easier to catch. We also see the GI [gastrointestinal] colitis and put some of our patients in the hospital for it. Those are probably more common.
I see a good bit of the endocrine symptoms. I do agree the GI colitis is common as well, and we also get a fair share of rashes.
MOLLY DAVIS, MSN:
I was going to say the same thing. [The] hypothyroid symptoms and rash are the most common grade 1 and grade 2 AEs [that I see], and then colitis is the most common grade 3 AE that I see.
I would agree with all that also.
What do you consider general best practice toward AE prevention, monitoring, and symptom management for patients receiving first-line combination systemic therapy for their advanced or metastatic renal cell carcinoma? At what timepoints do you check in with them regarding AEs? Do you ask about specific symptoms and, if so, which ones? What steps do you take to maximize a patient’s time on therapy?
We check in with the patients at every nurse practitioner, physician assistant, or doctor appointment. But we also, in the chemotherapy room, have the infusion nurses asking about specific symptoms, like how they’re breathing, if they’re having problems with the diarrhea, any new rashes, or any of the intolerances one would see with thyroid problems.
I think the best thing is the education and writing it down. I give them information that’s written for them to be able to follow, and encourage and insist that they call us anytime. We also give them little cards to present in case they go to the [emergency department], saying they are on an immunotherapy. We check very frequently because I find that a lot of the AEs don’t happen until 2 or 3 cycles down, including their liver functions and all of these things. When I meet with them, I go through every system. I don’t say, “How are you feeling, are you having any problems?” [I] ask them if they are having any headaches, any rashes, any nausea, to make sure that they’re tolerating it OK.
I agree that the education up front is the most important thing, and that patients should know what [the] general AEs are and what the critical AEs are that they need to call us with. An informed customer is always going to be your best patient. If they’re anxious over every AE because they don’t know, they’re calling you incessantly. But if they have that education and they know that you’re their resource, I think that they reach out, they communicate, and if they see you and know their team, you have a better handle on acute changes, worsening symptoms, and stuff like that.
From the cardiac standpoint, given that hypertension is an AE that can be seen across different therapies, what we do is, if patients have high-risk factors, the oncologist will get a pretreatment evaluation, and we optimize management of hypertension before initiation of these therapies. For those with several cardiac risk factors, we do a baseline assessment to prevent occurrence of AEs such as heart failure. Although with pembrolizumab it is very low—about 2.4%—pulmonary complications are common, and it’s hard to delineate whether it’s cardiac in origin or it is pulmonary. Whenever those pulmonary symptoms happen, [consults involve cardiology].
From the cardiac standpoint, we check the echocardiogram to see if there’s an increase in EF, which is not very common in terms of complications. Before these therapies are initiated, if there are several cardiac risk factors, we optimize management as well, and during therapy we monitor for signs and symptoms. Biomarkers are not very frequently used, although some oncology practices will use biomarkers. There’s not definitive data from research showing that the cardiac biomarkers are an effective way of screening. From our side, we do prevention as well as optimal management of the complications, particularly hypertension, which we most frequently see.
I would echo what all of you have said. The only thing that I try to hit home with patients, maybe not so much in the renal cell [population], is that people think the further out they get from the infusion, if it’s an immune drug, [that] the symptoms will go away. Symptoms can happen at any time. It doesn’t have to be the first few days afterward, and it will get worse if they don’t call us. It’s not like chemotherapy. Maybe it’s not as big of a deal in the renal cell population, but I think patients in general seem to think that the further they get away from the infusion, the symptoms will go away, but that really doesn’t happen with irAEs. They just get worse, and then they end up in the hospital because they didn’t call us right away. That’s one point that I try to make [to patients who are] on immune therapy.
What are the general counseling approaches that you use for patients getting first-line systemic therapy? How do you set expectations regarding the potential for dose reductions? In your experience, are patients hesitant to report AEs because they don’t want their therapy dose reduced, held, or discontinued? How do you engage caregivers in dialogue?
For all our patients who are starting first-line therapy, we typically enroll them in our digital home monitoring program that we have at Ochsner Health. Every patient is given a blood pressure cuff, a scale, and a thermometer. [It] integrates into our Epic system, and we’re usually able to monitor AEs and vital signs well through that. I make sure that they know how to work the program and understand that from the very beginning, depending on how they’re doing, dose reductions may be necessary. But I also let them know that the data support that. It doesn’t matter if the dose is reduced because for the data in those clinical trials, people had those reductions as well. I think people are scared about reporting them, but I think through our home monitoring program, we’ve gotten people more comfortable with acknowledging that they are having AEs.
That sounds like an amazing program that you have, and that they get this equipment through your institution is amazing. For patients, usually with dose reductions, we go over that everybody is different, and a different dose doesn’t mean less efficacy. Some people are a little bit more sensitive to a lot of things compared with other people, and we just need to find the right dose for the patient so that they’re able to stay on a course of treatment rather than having to do holds or discontinue due to AEs.
I think that it is not only about setting the expectations, but we want to make sure that they can get through it, because if the AEs aren’t being managed, then they end up having to stop the treatment. I think it’s important to pull caregivers in at the very beginning of education because they’re going to be the ones who [tell the patient] to call the doctor. Make sure that there’s a support system.
Which AEs do you find the most challenging?
I think the AEs that I fear the most are the cardiac ones. I loved hearing the commentary coming from our cardiooncology NP [nurse practitioner] because that is something that I have seen in my practice, and it’s very hard to distinguish.
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