Additional Advances in Immune-Related Adverse Events Research and Clinical Trials With Beth Sandy, MSN, CRNP

Oncology Data Advisor: Welcome to today’s episode of Oncology Data Advisor. Today, we’re here to discuss the NCPD activity that i3 Health currently has on our website about managing immune-related adverse events and the nurse’s perspective. I’m joined by one of our Editorial Board members, Beth Sandy, who is here to share some additional updates that have occurred in lung cancer immunotherapy as well as her perspectives in this area. Beth, thanks so much for coming on today.

Beth Sandy, MSN, CRNP: Thanks for having me, Keira.

Oncology Data Advisor: First of all, would you like to tell us if there have been any new updates in immunotherapy indications in lung cancer since this was recorded about a year ago?

Ms. Sandy: There’s been a lot in that past year. It’s great—in lung cancer, things are exploding all of the time. I’ll start with a new drug, tremelimumab, which was not yet approved a year ago. It’s an anti–CTLA-4 inhibitor. The only one that we had previously was ipilimumab, but now tremelimumab is approved in combination with durvalumab, which is a programmed death-ligand 1 (PD-L1) inhibitor, and in combination with chemotherapy. It’s a four-drug regimen for metastatic non–small cell lung cancer (NSCLC). It’s a crowded space; there’s so much immunotherapy approved in metastatic non–small cell lung cancer. I think with this particular regimen, the toxicity is a little bit more than what we would see with just chemotherapy and a single-agent programmed cell death 1 (PD-1) or PD-L1 inhibitor, but it’s still fairly manageable.

I think the interesting thing about their data is they had subset analyses in hard-to-treat populations like patients with KRAS mutations and STK11 mutations, where typically we have seen lower survival and lower progression-free survival rates. They had some compelling data in those subpopulations versus chemotherapy alone. In the lung cancer community, if we see one of those mutations, because KRAS is targetable but not until second-line right now, they have to progress on chemo and immunotherapy first. I think this four-drug regimen might be a niche in that population of patients, especially if the patient is fit and wants to be extra aggressive.

Another new drug that has been approved in the immunotherapy space in small cell lung cancer is tarlatamab, which is a bispecific T-cell engager. It’s interesting because these drugs have only been approved in the liquid tumor space. This is the first time in the solid tumor space in lung cancer and in small-cell lung cancer specifically, a very aggressive and hard disease to treat, that we’ve seen this drug get approved. It has a whole host of its own separate side effects that, again, people who are used to using BiTE therapies and chimeric antigen receptor (CAR) T therapies are used to dealing with. Now those of us in the solid tumor space are learning how to manage those side effects as well. The data is pretty good in small cell lung cancer; again, it’s approved in that second- or third-line setting, post-progression on upfront chemo and/or immunotherapy. It’s a tough space to treat and the data’s pretty compelling, though I will tell you the administration schedule is really difficult. We’re learning, but that is another new drug that’s been approved.

Then the other thing that I’ll mention is that—and there are other drugs that are not new but have been approved in a new space—is that we’ve really seen a big shift in the past couple years of moving immunotherapy to the neoadjuvant space, that preoperative setting. A year ago, nivolumab had an approval there. But in the past year, we’ve seen a significant approval and uptake in use of drugs like pembrolizumab and durvalumab, both of which have been approved in the past year in this space. These drugs are used in combination with chemotherapy in that new adjuvant space. We’re seeing really good pathologic complete responses and major pathologic responses. At the time they go to surgery, the surgeon has less disease to resect; there’s not nearly as much viable tumor coming out. I think the idea here is also that we can catch micrometastatic disease early. Boom, we’re getting these people on treatment right away, prior to going to surgery. Then with those two regimens, pembrolizumab and durvalumab, as neoadjuvant regimens and then in the adjuvant setting, they get just the immunotherapy. They get all their platinum-based chemotherapy in first. I think both of those regimens, are new and exciting. While the drugs aren’t new, it’s a new space where we’re using them.

Oncology Data Advisor: Awesome. It’s exciting to hear about all these updates that have occurred only within the last year or so; there’s definitely a lot going on in this space. Switching gears to immune-related adverse events a little bit, when you’re monitoring patients who are receiving immunotherapy, are there any particular risk factors that you keep in mind?

Ms. Sandy: There are things like autoimmune disease, and that’s probably one of the biggest things. That can range anywhere from mild eczema to Crohn’s and severe colitis that people may have. You have to really weigh the risks and benefits. I think this is another area where in the metastatic setting, we may be a little bit more likely to push the envelope because it’s not curative-intent therapy. But in that neoadjuvant and adjuvant space where we’re giving them curative therapy, especially neoadjuvant, we want them to get to surgery; that’s their curative-intent modality. I’m probably less likely to push those patients who may have bad psoriasis or significant colitis, like a Crohn’s-type disease, because I would be hesitant to give them such a bad immune-related toxicity that they can’t make it to surgery.

That being said, for well-controlled rheumatoid arthritis or well-controlled autoimmune skin conditions like psoriasis or eczema, things like that, I think I’m a little more likely to still give immunotherapy and monitor them. I go in with an eyes-wide-open approach and say to the patient, “Hey, we’re going to really have to monitor this.” Then outside of that, immunotherapy is pretty well-tolerated. Outside of those risk factors of autoimmune disease, we are giving this to most patients. Now, the other thing that falls into the autoimmune disease category is organ transplant. This is something that certainly in the neoadjuvant space I would not give to patients with organ transplant. I guess you can argue a little bit in the metastatic setting, but I certainly wouldn’t want to risk them rejecting their organ.

Oncology Data Advisor: That’s definitely good to know. One of the things that Blanca talked about in the activity was the importance of being proactive versus reactive when managing adverse events. Would you like to speak a little bit about that?

Ms. Sandy: I think it’s important for patients to know how the drug works. Without getting too detailed into the molecular biology of it, I talk to patients to say, “In general, your immune system becomes inflamed, and sometimes that can cause inflammation of really any part of your body.” Especially in lung cancer where we sometimes have higher rates of pneumonitis than other cancers, I’ll say, “If you’re short of breath or having a really bad dry cough, you need to call us.” You hope they would anyway, but you sort of give them that background. It’s hard to give patients a list of every single “it is” that can occur. A lot of times I’ll say, “If you have really bad diarrhea or significant shortness of breath, give us a call, but really anything can become inflamed. So give us a call if anything’s wrong. If you’re finding mild confusion, call us. If you’re having palpitations, call us. If there’s a minor rash that becomes a lot worse, call us. Just call us for anything.” And then I say, “We’ll tease it out and ask you more questions to find out if we think it’s from the immunotherapy versus something else.” I stay proactive in teaching our patients that way to call us and let us know.

Oncology Data Advisor: Absolutely. As new treatments are coming into practice, how do you try to stay up-to-date with supportive care strategies?

Ms. Sandy: I don’t know that supportive care has changed a whole lot with our run-of-the-mill PD-1, PD-L1, and anti–CTLA-4 drugs. Again, in general, outside of rashes where we’ll use topical steroids, oral steroids are often the treatment of choice for anything that’s symptomatic, like grade 2 or higher. Then of course, outside of the endocrinopathies—things like hypothyroidism, hypophysitis—those are things where we will supplement the hormone in question, whether it’s levothyroxine or hydrocortisone, whatever it may be.

One thing I’ll say here, like I mentioned earlier, is that we now have a bispecific T-cell engager, tarlatamab, approved for small cell lung cancer. That falls into this immunotherapy space. It is a T-cell engager. But with that, we’re seeing more CAR T– and BiTE therapy–type side effects such as cytokine release syndrome (CRS) and neurotoxicity such as immune effector cell–associated neurotoxicity (ICANS). This is something totally new to those of us who specialize in the solid tumor space, especially lung cancer, like myself. The CRS rate is pretty high, over 50% in these patients, so we’re starting to learn how to assess and manage CRS. ICANS is less common, about 5% or less, but it’s still something to know because if left unmanaged and untreated, it can become worse.

I think learning now about how to manage these types of things is important. We’ve been taught about these at other conferences, but some of us in the solid tumor space probably tuned out a little bit because we were like, “Oh, well, we don’t use those drugs. That’s all liquid tumor.” Now we are using them, so we have to be aware that outside of the “itises,” we now have CRS and ICANS that are associated with these therapies.

Oncology Data Advisor: Very important to know. So, as we wrap up, since this activity is geared toward nurses, do you have any advice specifically for nurses and nurse practitioners about what a critical role they play in treating and caring for patients receiving immunotherapy?

Ms. Sandy: Nurses and nurse practitioners are the first-line phone call. We have a whole triage nursing team where I work, and they are absolutely the first line. They know what questions to ask. It’s really important to know what questions to ask to tease out whether or not you think this is from immunotherapy versus something else, like from the disease or the chemotherapy. We need to make sure that we are going to our conferences, doing our online education, our webinars, podcasts, whatever it may be, to make sure we’re understanding what these new therapies are, why they’re being used, what setting they’re being used in, and understanding what to look for and then how to manage these toxicities.

Oncology Data Advisor: Absolutely. Well, thank you so much again for coming on today to share all these updates with us. It was great to hear about these new advances and your perspectives in the area, and I encourage everybody listening to check out the activity on the i3 Health website to hear more perspectives as well. Thank you again.

Ms. Sandy: Thanks, Keira.

About Ms. Sandy

Beth Sandy, MSN, CRNP, is an Outpatient Thoracic Oncology Nurse Practitioner at the University of Pennsylvania Abramson Cancer Center in Philadelphia, Pennsylvania. She specializes in the treatment and supportive care of patients with lung cancer and other thoracic malignancies. Ms. Sandy has authored and coauthored numerous peer-reviewed publications, posters, and book chapters, and has been a speaker at several national and international conferences. She is a member of several professional societies and is active on committees and editorial boards for APSHO, IASLC, MASCC, ONS, and SITC.