Integrating Adjuvant Therapy in High-Risk CSCC

The discussion turns to the role of adjuvant therapy for patients with high-risk cutaneous squamous cell carcinoma (CSCC), highlighting key findings from the C-POST trial. Through case-based discussion, the panel explores patient selection, treatment sequencing, and practical considerations for integrating immunotherapy into clinical practice.

This is Part 2 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: I think it's particularly important to have that recognition of who falls into the very highest risk category, especially since now we can do something about it, right? Now that we have the data indicating that the addition of cemiplimab after definitive local treatment can be helpful in decreasing further recurrences, then it's really important for us to try to be as precise as possible to ensure that we're capturing all the patients who could benefit from this. 

Dr Strasswimmer: So in a community setting, so at least an attempt at definitive resection is a standard of care and then postoperative radiation is a standard of care for these high-risk patients. So how about immune therapy and how does that work? 

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. A total of 415 patients were enrolled. The primary endpoint was a disease-free survival in the C-POST study, and the study demonstrated that the 3-year disease-free survival was 83.1% for patients who received cemiplimab compared to 60.4% in the control arm. 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. 

Immunotherapy now has an established role in selected high-risk CSCC patients. Patients receive a year of cemiplimab after completing surgery, surgical resection, and postoperative radiation. So cemiplimab is an anti-PD-1 inhibitor or an immune checkpoint inhibitor. So as an anti-PD-1 agent, these work by trying to turn on the immune system is the way I explain it to patients, so that your immune system can recognize the cancer and attack the cancer. And so now moving that into the adjuvant setting, patients complete a year of therapy and we saw that there's an improvement in disease-free survival with cemiplimab. 

Dr Patel: And then the other important exclusion criteria that we should talk about for immunotherapies is that solid organ transplant patients were excluded, which are typically not eligible for immunotherapy because of risk of rejections. 

Dr Wong: Yeah. So solid organ transplants, but other patients who have autoimmune conditions requiring systemic immunomodulatory agents also were not eligible for the study. And that's where I think real-world data and real-world experience is really important because in all of these phase 3 registrational clinical trials, the entry criteria, the eligibility criteria, are so strict by, necessarily so, right? Because we really need to be precise about whether or not a specific intervention is actually helpful and effective. But to your point, our patients don't necessarily align with the eligibility criteria of clinical trials. So what is it? How do we apply C-POST to your practice? Those are questions that are really important and that's where additional data is needed. 

I would love to glean the roundtable experts’ thoughts on my patient. This is a patient in his mid-60s with a prior history of multiple non-melanomatous skin cancers that were managed with local therapies, including Mohs surgeries, who presented with a squamous cell cancer of the skin inferior to the left side of the lip. He underwent Mohs resection, and pathology returned with completely resected tumor, negative margins, and no evidence of any sort of adverse pathologic features. Unfortunately, 6 months later, he self-palpates a left-sided neck mass, and a biopsy reveals that this is squamous cell carcinoma involving the lymph node. He undergoes an MRI of the neck. He's referred to head and neck surgery colleagues, and the pathology reveals metastatic squamous cell carcinoma in 1 of 14 lymph nodes. The size of the metastatic focus was one-and-a-half centimeters, and there was no extranodal extension. So this case was brought back to our tumor board for discussion as to next steps in treatment. And so from a radiation perspective, what would your thoughts and recommendations be? 

Dr Barker: So this is an interesting case because it is an example of regional metastasis of cutaneous squamous cell carcinoma, but this is probably the most favorable situation you'll see that. The involvement of lymph node is small, less than 2 cm, and there's no extracapsular extension. So this is a case where I think close observation would be a reasonable strategy, notwithstanding any other risk factors. 

Dr Wong: Ultimately, we presented the case in our tumor board, discussed in detail with the patient, and ultimately, he elected for close observation, and he declined adjuvant radiation. Unfortunately, a few months later, he re-presents with another palpable lymph node. He undergoes a revision neck dissection, and pathology reveals 1 of 2 positive lymph nodes. The size of the tumor is 2 cm in size and there was evidence of extracapsular extension. So now what? 

Dr Barker: I think the fact the patient's now recurred in the node base and the pathology's telling us there's extracapsular extension, I think the risk of further regional recurrence is relatively high now, I think high enough to warrant adjuvant radiation therapy. So that would be the suggestion. 

Dr Wong: And so the patient proceeds to complete adjuvant radiation, and following that, he was initiated on adjuvant PD-1 with cemiplimab. And he tolerated it well, and he completed a year of adjuvant therapy and now is I think 2 years in follow-up with no evidence of disease recurrence. 

Dr Barker: And I think all of the modalities that we represent, systemic therapy, surgery, radiation therapy, they play a role. They can help patients with CSCC. Does that mean that every patient needs every modality? No. There may be some patients for whom immunotherapy is contraindicated, it would be a bad idea. Some for whom surgery would be a morbid proposition, some for whom radiation therapy would not be a good idea. 

Dr Strasswimmer: And certainly some for whom in-office Mohs surgery is not appropriate. 

Dr Barker: Yeah. 

Dr Strasswimmer: Right. 

Dr Barker: So I think that the real challenge is recognizing the patients that would potentially benefit from each of these modalities. And so we have to be judicious about how we deploy these different treatment modalities for patients with CSCC.