Safety Monitoring in High-Risk CSCC

The roundtable discussion concludes with a review of the safety profile of adjuvant cemiplimab and best practices for monitoring and managing adverse events in patients with high-risk cutaneous squamous cell carcinoma (CSCC), with an emphasis on multidisciplinary follow-up, patient education, and long-term surveillance strategies.

This is Part 5 of 5:

• Part 1: Recognizing High-Risk CSCC
• Part 2: Integrating Adjuvant Therapy in High-Risk CSCC
• Part 3: Multidisciplinary Coordination in High-Risk CSCC
• Part 4: Applying High-Risk Criteria in CSCC Practice
• Part 5: Safety Monitoring in High-Risk CSCC

Dr Wong: So the C-POST study was a study that took patients who had high-risk cutaneous squamous cell carcinoma who had undergone and completed surgery and postoperative radiation and then randomized them one-to-one to a year of cemiplimab or a year, as compared to placebo. Overall, the safety of cemiplimab treatment was very tolerable, and side effects or adverse events aligned with what we know about side effects from immunotherapy and immune checkpoint inhibitors. Compared to placebo, overall, there were similar proportions of patients who had adverse events. Overall, very few patients had adverse events requiring treatment discontinuation. And for patients on the cemiplimab arm, there was a higher incidence of maculopapular rash as well as hypothyroidism, which is consistent with this class of anti-PD-1 agents. 

Dr Strasswimmer: Some of those side effects, particularly the maculopapular rash, we're not surprised. And as dermatologists, we can help to co-manage some of the skin-mediated events. 

Dr Wong: I think overall, fortunately, they were overall very relatively low-grade toxicities. Most patients who receive anti-PD-1 therapies, if they develop a rash, it's generally grade 1 or 2 and usually pretty easy to manage with topical steroids. Although I have had patients that over time, especially the pruritus and the itch, even though it's overall relatively tolerable, because of the chronicity of it can be more challenging long term. 

Dr Barker: I'm curious what you think about the immune checkpoint inhibitor safety profile that's been observed across different cancers and the fact that different cancers affect different populations. The CSCC population that's locally advanced is typically older than say, perhaps, a melanoma population. Do you see any signal that adjuvant immunotherapy is different in terms of safety profile in this population versus, say, others? 

Dr Wong: Actually, irrespective of the stage of disease or the patient's age or other comorbid conditions, I think overall these checkpoint inhibitors, including cemiplimab, are exceedingly tolerable. I have treated patients well into their 80s and 90s either in the recurrent and metastatic setting, but more so especially with CSCC, because these happen in older patients, in the adjuvant setting. And for the most part, patients are able to complete their intended therapy and most of the time patients come in, get their 30-minute infusion, hang out with us for once every 3 weeks or once every 6 weeks, and then go home and go about their day. 

Dr Strasswimmer: This was also quite a large study. So it's nice that you have that plus your professional experience with these patients to talk about the safety profile. 

Dr Barker: Yeah. The safety, I think, most patients, as you say, in my experience, seem to tolerate the treatment well. There is the, every once in a while, high-grade event that concerns me. 

Dr Wong: Right, and not all patients are the same. You have patients who have severe side effects that just assume that this is part of the plan. So they think that this is normal. And so I want to know as the treating oncologist when these things are happening, because patients don't have that perspective as to what's normal, what's expected, what's acceptable toxicity versus not acceptable. It's especially important when we're thinking about treating patients in the adjuvant setting where they may already have been cured from the local therapy. We want to be especially mindful about toxicities. Immunotherapy toxicities may not just be an issue acutely. They can have long-term sequelae. And so even though, again, in general, they're very well tolerated, with very mild toxicities, and most patients do fine, they're not without potential serious consequences. 

Dr Strasswimmer: It's been my practice ever since we had indications for immune therapy for locally advanced or metastatic cutaneous squamous cell carcinoma, we see these patients back in our dermatology practice. So even though they've had the visit from my other colleagues and maybe now they're under their main therapeutic intervention is from our medical oncologist, we see them back historically because we're in some ways the primary care doctor of their tumor. 

Dr Patel: Yeah. I'm very fortunate to have a really good dermatology colleagues that I can rely on, but a couple of other points that I want to ask you. A lot of immunotherapies have some rashes, maculopapular rash, we touched on that. Some strategies that you use to treat these side effects? 

Dr Strasswimmer: Today, in the era of immune therapy, we're beginning to think that this is basically the toxic skin changes of immune therapy. So it's the same biologic disease process. And fortunately, we have topical agents that we've known well. We also now have systemic agents that are FDA approved for atopic dermatitis, bullous pemphigoid, and so forth. So in coordination with the rest of the team, some of those systemic agents we can implement for patients on immunotherapy to mitigate that, which means they can continue to receive their important immune therapy. We co-manage the patients. 

Dr Wong: And I think that's a testament to the fact that our treatments these days are better. Patients are doing well, they're living longer. And so they do need that continuity of care with derma.... I don't think we're in the period anymore where we can just hand off the patient's care to the next person… 

Dr Strasswimmer: That’s right. 

Dr Wong: …especially in the area where we have multiple therapeutic options to offer.