Additional Advances in Non–Small Cell Lung Cancer Research and Clinical Trials With Beth Sandy, MSN, CRNP

Just under a year ago, Beth Sandy, a Thoracic Oncology Nurse Practitioner, co-led a continuing medical education (CME)/nursing continuing professional development (NCPD)–approved activity, Harnessing Immunotherapy-Based Strategies For Advanced Non–Small Cell Lung Cancer (NSCLC). In this interview, she provides an update on advancements made in treatment and supportive care strategies since recording.

Oncology Data Advisor: Welcome to Oncology Data Advisor, a digital resource for the multidisciplinary cancer team. Today I'm joined by Ms. Beth Sandy, a Nurse Practitioner at the Abramson Cancer Center at the University of Pennsylvania. Recently, she recorded an educational activity with us regarding updated strategies in treating non–small cell lung cancer. She's here to update us on changes, resources, and new strategies since recording, and why it is vital for the health care team to participate in these educational activities.

Thank you for joining us again, Ms. Sandy. Would you like to introduce yourself and talk a bit about your research and what you do?

Beth Sandy, MSN, CRNP: Yes, thanks. My name is Beth Sandy. I am a Nurse Practitioner in Thoracic Oncology at the Abramson Cancer Center at the University of Pennsylvania, in Philadelphia. I've been a Thoracic Oncology Nurse Practitioner for 20 years. I speak a lot about lung cancer, and I have a lot of editorial duties and chairing of conferences, mostly related to lung cancer, so thank you for having me back.

Oncology Data Advisor: Awesome. Great to have you again. So, first question I have for you is, since recording the activity, have there been any updates on supportive care strategies for NSCLC or results from clinical trials you would like to highlight?

Ms. Sandy: Yes, I think in our program, we went through everything that was approved for non–small cell lung cancer as far as immunotherapy approaches. The one major thing that was approved since our program is the POSEIDON data. So, this is really a new frontline regimen for patients with either adenocarcinoma or squamous non–small cell lung cancer, and this is really a unique regimen, because it's four drugs. So, here you have a platinum-based doublet, which is the cornerstone of everything that we do, but then adding both durvalumab and tremelimumab (treme). These are two different checkpoint inhibitors, so it's a four-drug regimen.

Tremelimumab is a new agent, new to the market. I think it initially got approved in one of the gastrointestinal (GI) indications, but then just right after that, in lung cancer. It is an anti-CTLA4, and in this regimen, you get four cycles of all four drugs. With the fifth cycle, they actually drop the tremelimumab and do only durvalumab, and then with the sixth cycle, you get both the tremelimumab and durvalumab again, and then you only go on to receive durvalumab in the maintenance setting. So, it's a fixed dosing of only five actual cycles of treme. The dosing is a 675 mg flat rate, and I think what a lot of us think about in thoracic oncology is that, "Okay, here's yet another regimen of chemotherapy with immunotherapy. Where does this fit in?"

Here's what I would say about it; It is the only regimen where you can get four cycles of platinum-based chemotherapy plus dual checkpoint inhibitor. So, if you're looking for a really aggressive approach, especially in certain populations where maybe they've just progressed on a single-agent immunotherapy, and you want to try a dual approach, something like that might be appropriate.

The other area they have data in, which is very interesting, that we don't see in the other trials with immunotherapy, is data in our patients with Kirsten rat sarcoma (KRAS) and STK11 mutations. KRAS is one of the most common things, and they parsed out their KRAS population, not just the G12C, but all KRAS, and they typically have a little bit of a poorer prognosis on average. What they found was that with the POSEIDON regimen, they had a 25-month overall survival versus 10 months with chemotherapy alone. So, 25-month overall survival is actually pretty good in that population of KRAS-mutated patients where they tend to do poorer. I would point that out.

The STK11, again, is a poor prognostic biomarker that we know about, and that population had a 15-month overall survival as opposed to 10 months on chemotherapy—maybe it was even less, might have been nine months on chemo—but either way, they tend to do poorly, so they did actually better than all-comers in that regimen. So, it seems like maybe with these poor prognostic biomarkers, perhaps you need a stronger immunotherapy approach. I think that remains to be seen, but this is the one new, big regimen that was approved since we did our programs. I think it deserves some discussion, though I don't necessarily think this is something everyone should automatically get just because it's four drugs. I still think the other regimens that we're used to using, especially just the three-drug regimens with one immune checkpoint inhibitor, are still very reasonable. They probably have less risk for toxicity, financially more cost available, just as good of data in the all-comers, but possibly in these niche areas, this may be an area to consider using the POSEIDON regimen.

Oncology Data Advisor: Awesome, this is brilliant information. I really appreciate it. Why would you think it's important for clinicians to understand these results and stay updated on these new treatments for NSCLC?

Ms. Sandy: Well, because there's data coming out like wildfire, especially when it comes to immunotherapy. We're going to talk in a minute here about future immune checkpoint approaches, none of which have been approved yet. These that I just talked about are the old ones. It's still programmed death-ligand 1 (PD-L1) and anti-CTLA4, but I think it's important to kind of know now, looking at some of these trials, where they're able to look at different biomarkers and how those populations may fare better with one or two dual checkpoint inhibitor therapies as opposed to only one, this becomes more important. So now, in a patient like this, maybe where there's STK11 or a KRAS G13D or G12D—one that's not targetable—you might still say, "Oh," but this might actually make sense, because I know that there are data there that they did better with this one regimen. So, I think it's making us look at biomarker reports more closely, even when there's not something necessarily actionable.

Oncology Data Advisor: Going back to what you said, what we would be mentioning, are there any current clinical trials or studies you're keeping an eye on, or even participating in, that you would like to mention?

Ms. Sandy: Yes, so let's talk about the future of lung cancer, which, no surprise, is mostly immunotherapy. Before I get to that, I mean targeted therapies, yes. We now have pretty much nine unique targets that we have targetable therapies for, and even within those, like epidermal growth factor receptor (EGFR), there are the EGFR common mutations, and then there are the uncommon mutations and the exon 20 insertions, which all have different approvals. So even within some of our known mutations, we have heterogeneous mutations that we may treat differently. So, it's very exciting.

I think in the targeted realm, we will still find more targets that we can then develop drugs to treat. That is definitely something in the future, but I think truly, where we're going to find the biggest leaps and bounds of differences will be in immunotherapy approaches. So, I'm going to talk about five different ones.

We did cover this in our program with T-cell immunoglobulin and ITIM domain (TIGIT). So TIGIT is an immune checkpoint that interacts with CD155 on antigen-presenting cells, and it downregulates T cells and natural killer (NK) cells. Again, when this is present in tumors, it's tamping down the immune system can't kill a cancer. There are 15-plus different molecules in development here, and that is a lot. This is an exciting field. A lot of people are looking at this target.

Now, I don't know that there's going to be as much single-agent data here in this, but it's all about combinations, and that's what you'll hear me talk about with the other ones. It's all about combinations, putting different checkpoints together. So, I think TIGIT is an exciting checkpoint. I think it's going to need to be combined with probably another immune checkpoint, plus or minus, maybe chemotherapy. We will see, but this is something that's pretty far in development now. I think the name of the trial was CITYSCAPE. We did cover it in our program. There's been some updates to it. It looks very promising, in combination with PD-L1 checkpoint inhibitors. So, if you didn't see it, check it out in our program, and there's updates to come.

The second one I'll talk about is lymphocyte activation gene 3 (LAG-3). So LAG-3 is another immune checkpoint for which there are several drugs that have been developed. Interestingly, some of them are monoclonal antibodies. There's actually another one too that's not a monoclonal antibody, that kind of has a different delivery system, I think more based at the antigen-presenting cell as opposed to on the cell surface. Again, it's another one that we're doing clinical trials with, that we have done clinical trials with at Penn. We are looking to combine this checkpoint with another checkpoint inhibitor to get the responses, but this is something that's also fairly far in development.

Another one that I would talk about is GITR, or "gitter", we call it sometimes. So, this is glucocorticoid-induced tumor necrosis factor receptor–related proteins—there are a lot of words there. This is mostly preclinical. A lot of these drugs are not yet in clinical trials. Maybe some are starting, but this is another one. Again, this is looking at just a very different way of targeting the immune system and the tumor cells. So, it's something just to keep in your mind.

Then the fourth one I'll talk about is chimeric antigen receptor (CAR) T. So, it's not a new concept. CAR T is approved now in several different lymphomas, multiple myeloma. I think in solid tumor, we haven't gotten approvals; there are a lot of technical difficulties. What are we targeting? Then when we try to administer it, we're getting all of this trouble and side effects and issues. There are a lot of technical things we have to work out, but we're not giving up hope on this. We've been trying to trial this. I know we had a trial at Penn in lung cancer, and we couldn't really enroll people, because it was almost nearly impossible to enroll them, again, just based on a lot of technicalities that we're trying to work through and figure out how these best fit in that solid tumor.

I said five, but I think I had four, so I miscounted, but those are the four that I'm excited about in the future. Again, the take-home message—outside of CAR T—the take-home message is combining these different targets with already known targets, like PD-1, PD-L1 checkpoint, anti-CTLA4, and then just looking for new pathways for us to develop.

Oncology Data Advisor: Awesome. This is great information and definitely a lot of things to look forward to, which is great. So, I wanted to ask you, and I know you kind of just touched on it, but if there are any milestones that you are particularly looking forward to or hopeful to see completed or started in treatment by the end of 2023?

Ms. Sandy: I don't know. I wish I had a crystal ball to say, because sometimes I would hate to predict that, because I think a lot of times, especially with clinical trial drugs I've seen. Take tremelimumab—we just talked about that—which is now approved. We've been trialing that for a long 10 years, probably, and I thought, "Wow, I guess that drug's never going to come around," and then here it made its way into 2022. So, I hesitate to say which one. I think TIGIT is probably the one furthest down the line, and maybe the next one that's likely to get some sort of approval in a combination setting, but I never know. You don't know, and there could be one that suddenly gains progress really quickly, especially like GITR coming out of the preclinical models, mostly mouse models right now, but looking really promising. So, we just never know.

Oncology Data Advisor: Right, definitely, and final question I have for you is, as we're ending the interview, are there any resources that you think would be beneficial for clinicians that are listening in to help them stay up-to-date and help them stay on top of these new strategies and, like you said, the rapid-fire updates of things that are going on?

Ms. Sandy: There are lots of resources out there, different conferences that you can attend. Obviously, we like our presentation as well. The one thing, though, I did want to end with is supportive care. This is something that I had presented on in our original conversation, and people are always saying, "Well, what are the updates in supportive care for the toxicity management of immunotherapy?", and realistically, I can't say, "Oh, it's magically new." We have our immunosuppressive drugs that we're still using, things like prednisone and then infliximab and other immunosuppressive drugs. So, that really hasn't changed, but what I would say is that the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) both updated their supportive care guidelines in 2022, and probably are likely going to do it again in early 2023. So, these are really the best resources to go to when you're worried about how to work up and manage some of these patients, especially some of the rare toxicities. If you go, both ESMO and NCCN even have guidelines on how to manage some of the more uncommon ones, let's say, like the cardio toxicities that are uncommon. So, I would really use those as good resources.

I think the one thing that I've sort of done more in the past year relates to colitis, and I've been tending to use the fecal calprotectin test more often. It's a send-out stool test, so it's a little bit inconvenient in that respect, but such a good marker for inflammation within the bowel, and really helping me understand where the colitis is at as I'm tapering and treating, as opposed to having to do invasive procedures. We're hardly even doing that anymore. Initially, it was all about colonoscopy and doing all this. I don't know about other institutions, but mine takes a long time to take a colonoscopy to be scheduled and figured out. By that time, their colitis might be resolved. So, I've been using more of the fecal calprotectin. I think that would be one of my take-homes over the past year, but from supportive care, not huge changes other than that. It can be complicated. Look at those guidelines, especially ESMO and NCCN. They're updating them every year, sometimes twice a year, with the most up-to-date information.

Oncology Data Advisor: Great. Well, thank you, Ms. Sandy, for all this research and updates, and thank you for your time today. I really appreciate it.

Ms. Sandy: Thank you for having me.

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.

For More Information

Cho BC, Abreu DR, Hussein M, et al (2022). Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study. Lancet Oncol, 23(6):781-792. DOI:10.1016/S1470-2045(22)00226-1

Transcript edited for clarity. Any views expressed above are the speakers' own and do not necessarily reflect those of Oncology Data Advisor.