Pam Profusek, RN, MS, discusses how to manage the AEs associated with immunotherapy agents, like durvalumab.
Pam Profusek, RN, MS
Results of the clinical trial which lead to the recent FDA approval of durvalumab (Imfinzi) showed that the PD-L1 inhibitor was well-tolerated in patients with locally advanced or metastatic urothelial carcinoma.
The single-arm trial included 182 patients with locally advanced or metastatic urothelial carcinoma who experienced disease progression following platinum-containing chemotherapy. In the study, the objective response rate (ORR) per blinded independent central review was 17.0% (95% CI, 11.9-23.3). At the data cutoff, the median duration of response was not reached (range, 0.9+ to 19.9+ months). Among 95 patients with high PD-L1 expression the ORR was 26.3% (95% CI, 17.8-36.4). In the cohort of 73 patients with low or no PD-L1 expression, the ORR was 4.1% (95% CI, 0.9-11.5).
All-grade adverse events (AEs) occurring in 15% or more of patients included fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, and urinary tract infection. Grade 3/4 AEs occurred in 43% of patients. Infection and immune-related AEs observed with durvalumab included pneumonitis, hepatitis, colitis, thyroid disease, adrenal insufficiency, and diabetes.
In an interview withTargeted Oncology, Pam Profusek, RN, MS, research nurse coordinator, Cleveland Clinic, discussed how to manage the AEs associated with immunotherapy agents, like durvalumab.
TARGETED ONCOLOGY:What are some of the considerations taken when deciding if a patient can receive immunotherapy?
One consideration would be if they already had their platinum chemotherapy, whether it be cisplatin or carboplatin. You have to consider if they already had that and if they have progressed, because these drugsexcept for atezolizumab—are for cisplatin-ineligible patients, so they can get this immunotherapy as a first-line therapy. But for durvalumab, you have to have already progressed on a platinum agent. That's 1 consideration, have they had their platinum yet? Have they progressed, or are they still OK from their chemotherapy?
Another consideration would be if they have a history of an autoimmune disorder and what it is. If it's psoriasis and it's not acting up, you might think differently than if it was Crohn's that they are currently being managed for, or if they have currently active multiple sclerosis. There are different levels of autoimmune disorders. That might be a consideration, and that's something that would have to be discussed with the patient, too, as to the risks associated and if we could possibly make those disorders worse.
The reason I'm saying “could we possibly” is because active autoimmune disorders were not part of the durvalumab trial, so if they were actively getting treated and it was severe enough, those people were excluded from the trial that got this drug approved. None of the trials so far for immunotherapy have included people with autoimmune disorders, as it was still an experiment and we didn't know what kind of reactions we could get, so we excluded them.
TARGETED ONCOLOGY:What are the toxicities associated with immunotherapy agents, such as durvalumab?
For an immunotherapy drug, like durvalumab, we are taking the breaks off the immune system. The parking break is on there for a reason, which is so that we don't get autoimmune disorders. Any time along this treatment plan, whether it be cycle 1, cycle 50, or a year or 2 after stopping taking the drug, we can create an autoimmune disorder, or an autoimmune reaction in the person that is currently receiving or had received an immunotherapy drug.
We can't say exactly when it could start. You may get 1, you may not get 1, you may get more than 1. It can affect any part of the body, whether it be the skin, liver, heartthe heart is kind of rare—kidney function, liver function. We can create type 1 diabetes, we can create hypophysitis, which would be the inflammation of the pituitary gland. Any of these “-itises” can happen with this class of a drug.
TARGETED ONCOLOGY:How can the toxicities associated with immunotherapies be managed?
We manage those 2 ways. One would be if we need to, we can hold treatment. There is no dose reduction for durvalumab. Let's say for elevated liver enzymes, for example, we can hold treatment and see if those improve over the next couple of weeks. If they improve to a grade 1 level, we can go ahead again. If it were type 1 diabetes, we would have to manage that with insulin, just as if it was someone who was born with type 1 diabetes.
If it has to do with 1 of the endocrinopathies and we need to manage it at a certain level, then we might have to use a steroid. Think about it like this: let's say when you get a bee sting and you're allergic to it, you have to use an EpiPen to reverse the effect. This is something similar to that, where we are taking that break off of the immune system, and by giving a steroid, we're putting that break back on, and saying to the immune system, calm back down. If the autoimmune reaction is high enough, we might have to initiate a steroid. If not, we can buy some time and see if it improves. If it's a rash, and it's mild, we can use topical creams. If it gets a little worse, we can maybe then institute a steroid cream. If we had to, we could then initiate steroids that are systemic, so it depends on what effect it is, and how bad of an effect, but generally it's treated with a steroid.
TARGETED ONCOLOGY:What is a nurse's role in addressing these toxicities with patients?
I like to describe the mechanism of action and how it's different than chemotherapy, since they know what kind of results or what kind of side effects to expect. It's different than in chemotherapy, where we are killing all cells that are replicating fast, so it could go after your hair, the lining of your mouth, and your stomach, or it could make ridges on your fingernails and things like that, that's why they're seeing a certain kind of side effect. If they understand the mechanism of action for immunotherapy, then it can explain what kind of side effects they might see, and that we don't know when these might occur. We like to tell nurses to encourage patients to tell us any kind of side effects they're having so that we can act on it early and manage it ahead of time so we don't have to delay treatment as much, while we can still manage them, so we can keep giving them their treatment.
One of the things I like to tell nurses is to make sure they get a baseline of what their patients’ bowel movements are regularlyis it once a day, twice a day—because managing colitis or recognizing if you have that problem is determining how much over and above the usual are you having now. It's good to know what the baseline characteristics of the patient are to know if you're in trouble or not.
We also let the patient know to tell us if they're having any shortness of breath or any trouble breathing or coughing. The same thing with diarrhea, let us know. Rashes and things like that we can manage when we see the patient, but we let them know first, if you think you need to go to the emergency room for anything, go to the emergency room. It doesn't mean that because you're getting immunotherapy for cancer you can't also have a heart attack. There are things that can happen to you that require an emergency room visit. However, if it's something like shortness of breath and you've already talked to us, we'll likely call the emergency room physician and let them know this person is on an immunotherapy, and they might have pneumonitis. Maybe they do have pneumonia, maybe it is a pulmonary embolism, but you need to rule out pneumonitis and that would be by looking at a CAT scan and seeing if they have a snowstorm on their CAT scan or ground glass.
We like to give them information of what possible side effects we could cause, so that they know to let us know when we're getting into trouble. We let them know these are rare side effects, but they can happen. Especially, once they progress off treatment, you need to let them know this can happen a year or 2 years down the road. It can happen late, so it's always important to have a card in their wallet saying what immunotherapy they're on if they're going to a local hospital that doesn't have everything on their electronic records.
TARGETED ONCOLOGY:What would you say the challenges are with treating patients with immunotherapy?
It's actually kind of a joy to treat them with immunotherapy, because before we had this, there was not much hope and not very good outcomes. It's been a total paradigm shift for us.
These immunotherapies do not work for a majority of patients. However, when they do, the results can be amazing and durable. Only time will tell just how long the durability will be.
I think the hardest thing is getting cocky with some of the patients that do well for 1 or 1.5 years of being on treatment, and then all of a sudden something sneaks up and it's kind of like do I have an autoimmune reaction going on or is this just bad Chinese food or something?
We had a patient on the trial that got atezolizumab approved, and at cycle 45, which is a couple years in, he had 0 side effects up until then. Then all of a sudden, he got pneumonitis. That can be a little tricky when, in essence, these immunotherapies are so well tolerated that you become too confident and then all of a sudden something can pop up and you're not expecting it. Whereas, you maybe get used to chemotherapy more where you know you're going to dip down, their white count is going to go down, you could get the infection. It gets really predictable and you know what you're seeing all the time, whereas these people can coast and coast and then all of a sudden something comes up.