Identifying The Appropriate Patient for IO Therapy in Advanced Non-Melanoma Skin Cancer

In this segment, expert faculty explore the clinical considerations involved in selecting patients with aBCC and aCSCC for IO therapy. Topics include evaluation criteria, comorbidities, patient characteristics, and the shared decision-making process between clinicians and patients when determining the suitability of IO therapy.

This is Part 2 of 4:

• Part 1: The Role of IO Therapy in ​Advanced Non-Melanoma Skin Cancer
• Part 2: Identifying The Appropriate Patient for IO Therapy in Advanced Non-Melanoma Skin Cancer
• Part 3: Real-World Case Studies and Insights on IO Therapy for Advanced Non-Melanoma Skin Cancer
• Part 4: Operational and Logistical Considerations With IO Therapy for Advanced Non-Melanoma Skin Cancer

Dr Oliver Wisco: All right, so let's just change directions a little bit. Obviously, we have a lot of experience with the—we've had a lot of discussions about the background, where we're going with this, indications. I'd love just to hear a little bit more about your guys' thought process for patient selection. Once again, for you, too, George, with such experience with already infusing in your clinic, I'd love to hear the thought process of who comes to you? Who are the people that you say, I definitely need to start considering infusions with this medication with these patients? 

Dr George Murakawa: So, it comes two ways. Some of our patients are referred by other dermatologists because we already know how bad it is. And no issues there. And we put them on as necessary if appropriate. And then, we start working up patients. And then, once we realize that, the extent of their tumor, then we have to go through the work of getting them approved for cemiplimab. Now, probably the most critical issue if you're ever going to infuse is, it's based on insurance, insurance, and insurance. And you have to go through all the benefits. You have to know what they can get, whether you can get them a free drug through their programs or whether it’s a buy and bill or whether it's through their pharmacy benefits. But you have to work that out. The technical part of actually doing the infusion, that's pretty straightforward. But whether we do it or we send someone else, we still have to do all the work. And we still have to do all the management. And we still have to take care of everything. 

And that's a large part why we've found it's much easier for us to infuse the patients ourselves. And so, that's how we view it. And the patients are happier. We take really good care of them. In a lot of infusion centers, they just rush them in and out. We've had patients who are on infliximab. They get 11 vials shoved in them in under an hour. And we would do it probably at about 3, 4 hours plus because that's a lot of infliximab. And they would tell us that when they went, they'd feel miserable for at least a week-and-a-half, because there was so much. They just felt so nasty. So, in general, I think we do a better job when they are in our space than when we do it other places. And then, on top of when we sent to infusion centers, they don’t—the hospital ones don't have a physician on hand, and any issues they send us anyways. So, we find that care is better if it stays with us. 

Dr Oliver Wisco: Thinking about the patients and for selection, obviously the logistical piece is so critical. Todd, would you like to just summarize when these patients come through, your thought process of working through the guidelines and getting them to this space where we're now talking about multidisciplinary care and your decision. Where is it in the care process that you say, okay, this patient really should be considered for these therapies? And right after that, I'd love to talk to Jason about thinking about the patient selection from the perspective of: how do we optimize who we're selecting from the potential side effect perspective. 

Dr Todd Schlesinger: Yeah, so I think it's a great question. And it really brings back into that multidisciplinary team and that this is not a practice I do alone. So, if I have a patient who I'm considering for immuno—now, I don't infuse like George. I think he's a model for infusion. I think it's amazing. And I learned so much from all you guys, especially the infusion piece. I think because there's a lot of setup involved and a lot of work involved in having that in your office. And then, the risk of all the things you mentioned. But when it comes to thinking about the patients, first, if it's going to be a discussion with the patient, that's the first thing. We're going to talk overall, just pluses and minuses of the therapy itself and things they can expect and whatnot. But then, in my case, I'm going to want that patient to be seen by oncologists as well. 

What do they think about it? There's going to be imaging involved. There's going to be lab work involved. We're going to make sure we know the extent, depth, and breadth of that tumor. We are talking about metastatic tumors here. We're talking about serious cases of cancer. And I'm not going to just be managing those patients in my clinic and not talking to anybody else about it. In my case, it doesn't mean I wouldn't be comfortable prescribing the medication, having it infused, doing that thing. But when it comes to, I want the radiation oncologist too, and sometimes it just might be a phone call. Hey, I've got this patient. Here's where the tumor is located. Some cases it's easy. And we'll talk about when we get to the cases. We'll talk about some cases are, this is a hands-down winner. This one, maybe we should try something else first. Maybe we should. So, I think that's a lot of discussion with the MDT before we make that decision. Of course, the patient's at the center of that decision-making. And then, all these things, characteristics of the tumor size, location, all those things come into play. Big decision. I call them inflection points in care when you're making—either starting a new therapy or switching therapies. These are big changes in the pace. It's going to affect their life. So, that's how I go through that process. 

Dr Jason Hawkes: And, just adding, can we look at these patients and say, these are not the right drugs for you? It's difficult because we're looking at the tumor cancer characteristics. And in the situation where they might have other—a whole history of other things in their past or even current conditions. The problem with this group is that, so far, we haven't been able to predict: this is the patient who's going to get pneumonitis. This is the patient who's going to get colitis. But I think the theme that comes out in this group is that these are essentially autoimmune processes, right? This is your immune system attacking the body or the tissue or these different organs in response to preventing the ability of the immune system to shut it off. So, I think one of the important factors, one, we need to know whether for the surgeons, for example, whether you're managing psoriasis or eczema or these other autoimmune conditions, you need to be aware of those patients that might have those. Women, we know, have a much higher rate of autoimmune conditions for a lot of reasons we won't get into, but we need to watch that group. 

We need to watch groups that clearly have preexisting diseases, particularly those that have uncontrolled diseases, right? So, it's very different if you had a psoriasis patient who had one of these tumors that was on a therapy that was controlling their disease as opposed to somebody who had untreated disease, right? But, again, even if we watched in the history, we say, okay, well there's a 38- to 40-year-old with no autoimmune history, no other chronic inflammatory conditions or itching. They're still at risk for one of these adverse events. So, I think one of the silver bullets to this work will be, can we start to predict those people that will have certain adverse events? And then, later, we can talk a little bit about how do we abrogate those responses or control them without working against the cancer piece? So, I think one, these patients can happen. They can develop any of these side effects even with no hint that they were going to get them. 

And then, there's others. I remember being at Rockefeller when, right across the street we had MSKCC. And these patients would often come to us in dermatology who are in therapy. And they'd come see us for worsening of their preexisting psoriasis. So, there's some that we might predict this can happen. So, it's also setting the expectation with patients to say, you may experience worsening of these conditions, or you may develop some of these conditions, but we're going to try to walk that balancing act. So, I think, knowing the ones that are there are helpful. But even when we're detailed, there's going to be cases that pop up that you wouldn't expect or predict. And surprisingly, people that have these conditions don't always flare, which is really interesting. So, you can have an underlying history of psoriasis or eczema or vitiligo and see a good tumor response and not have worsening. We don't understand that yet. So, I think there's still a lot to be learned in terms of what's happening from the biology. 

Dr George Murakawa: I think, in the past, with the large basal cell carcinomas, when you'd have the discussion with them for treatment and you'd talk to them about vismodegib, they're absolutely apprehensive to take it because they know that they're going to have side effects. And we tell them, well, if there are, you could stop it. But now, we could say, well, we'll start you on it, but you can quickly move forward. And if you're having any of these issues, it's no longer your only option. And they're much, much more receptive to it than they used to be. 

Dr Oliver Wisco: It would be great, as we start moving forward with expanding our use, everything for understanding who's going to be the better responder to also understanding who's going to develop the adverse events. Obviously, a huge area that we need to move towards. 

Dr Todd Schlesinger: I was just going to say a couple more things about vismo and sonidegib, were both approved for basal cell carcinoma as well, is that for those drugs, we have gotten smart. So, we're better at preempting the adverse events, which we're also getting smarter with immuno-oncology, preempting the adverse events potentially even in high-risk populations, that were transplant patients, so that we would think normally we couldn't use them for. So, that's one thing. We're getting better at keeping them on therapy longer, even with those drugs. The second thing that Jason was mentioning is—has to do with talking about the adverse events and how we can predict those. We also can use those to predict the outcome. So, in some cases, we know certain adverse events are actually associated with a better outcome rate, better overall response rate.

Dr Jason Hawkes: Like vitiligo in the melanoma trials. 

Dr Todd Schlesinger: Right. So, for these drugs, it's dermatitis. So, actually, when I see dermatitis, I'm like, okay, this is great. I welcome it because that dermatitis means that that drug's having an effect. If I see hyperhidrosis, I'm not welcoming it because hyperhidrosis patients that develop whatever, they tend to have worse outcomes. So, there's a study recently published—well, it's not that recent, in JAMA—that looked at some of those side effects. Journal of American Dermatology—actually, it was in JAMA, JAMA Dermatology, that looked at the adverse events across the board of multiple different adverse events and stratified the overall odds ratio, odds ratio of having a good outcome or worse outcome depending on what adverse event they had. So, that's something we also have to learn more about. And when you're managing these patients early on and what side effects you're looking to, almost like looking for, I want to see that. Because that means my patient might have a response. 

Dr Jason Hawkes: Yeah. I've heard someone describe this as kind of like a vaccine. You're given a vaccine and you want to see an exaggerated immune response. So, we give them this therapy and we want to see that immune response ramp up. Because that’s the hope that it ramps up and hits the tumor, right? So, it's that same concept. 

Dr Todd Schlesinger: It's the nuance of it when you start treating the patient. 

Dr Jason Hawkes: Yeah, we want to see it. And when people don't have a response, we're like, are we going to give that protection? Or in this case, are we going to get the immune protection against the tumor? So, the lack of a response raises that question mark, these robust brisk responses in immune activation. Yeah, it makes sense where, yeah, if those cells can hit some of these tumors, then that can be a sign of that early response. 

Dr Oliver Wisco: Thanks so much. So far, guys, this has been an amazing discussion. Everything from understanding the mechanism of action, thinking about why these immune adverse events occur, thinking about the indications, and how we manage these complex cases.