Locally Advanced CSCC: Post-Immunotherapy Strategies

Michael R. Migden, MD:It’s not an easy decision about what to do next when immunotherapy fails. I had a patient who had some apparent pseudoprogression, but that was followed by [a] significant decrease in the size of their lesion, and then we thought things might be heading [toward] complete response. On 1 side of the original target lesion area, there was a new tumor growing, and it was found to be squamous cell. That tumor, for unknown reasons, wasn’t seeming to respond. But the fact that the patient had a much smaller tumor than when he first saw me and when treatment was first initiated meant that we could go back to the head and neck surgeons, and they had a tumor that was much more resectable with a higher confidence of painting clear margins.

In terms of patients who progress with limited options, there’s not a lot right now. The question is, in the future, could combination therapy and anti-PD-1 [anti-programmed cell death protein 1] plus something else actually be effective in cases where an anti-PD-1 alone may not be? That’s an area of potential investigation. If we think about returning patients to old therapy, which would be systemic therapy of chemotherapy or the EGFR-targeted agent category, you have to think about the lower tolerability, the higher rate of adverse events, whether the patient can stay on that therapy, and the lower response rate typically found in those therapies compared to immunotherapy.

The prognosis of people who have a complete response on immunotherapy such as anti-PD-1, cemiplimab, or others, is good. But the data are limited. We have case reports where people have had durable responses. We had the initial data from the phase II trial. We don’t have years and years of follow-up at this point in terms of any sizable population, so it remains to be seen what the true prognosis is. I’m very encouraged by the results that I’ve seen so far in that I have multiple patients who have had complete response. Many are off therapy now, and they still have no evidence of any disease, so that’s very encouraging. That’s not definitive. Until we have longer interval follow-up data from these trials, it’s hard to say with certainty.

The recommended follow-up after treatment concludes is basically standard-of-care surveillance if the patient has had a complete response. If they hadn’t had a complete response, it would be standard of care follow-up to check on the status of their tumor. I’m thinking in terms of checking once a month for some period of time and then reducing the frequency down to every 2 to 3 months. If the patient has a complete response and they’re a couple of years out, we can spread that to 4 to 6 months. That’s the interval that I think of in terms of follow-up. Of course, it depends on how complete their response was and how far out they’ve been.

Transcript edited for clarity.

A 69-Year-Old Man With Advanced CSCC

• History and physical exam
  • An otherwise healthy, 69-year-old male, fair skinned, retired construction worker, widow
  • Presented to his PCP with what he described as a wound that was not healing behind his ear; he reported first noticing it at least 6 months ago and complained of recent onset of numbness in the area.
  • ECOG PS 1
  • The visible, ulcerated lesion was 4.5-cm in diameter and >5-mm deep
  • No palpable nodes
• Biopsy confirmed a poorly-differentiated, infiltrative, postauricular cutaneous squamous cell carcinoma lesion with 7-mm invasion into subcutaneous fat.
• The recommended definitive surgical approach involved partial auriculectomy; the patient declined.
• Cemiplimab 3 mg/kg q2w was initiated