Treatment Approaches in Non-Melanoma Skin Cancers - Episode 9
Drs Bakst and Cohen close out our second clinical case scenario by providing their thoughts on potential radiation therapy and using cemiplimab.
Glenn J. Hanna, MD: Dr Bakst, for the same case, you’ve got your surgeon’s input evolving. Maybe you can comment on this particular scenario, what you’d be thinking about when you meet the patient in terms of radiation.
Richard Bakst, MD: It’s all about appropriate stage: how deep is the lesion? Is this something that can be conceivably treated with superficial radiation, like electrons, or are we concerned about deeper spread, where we use traditional IMRT [intensity-modulated radiation therapy]? Are there nerves involved? If they all are, then that changes the whole dynamic of the radiotherapy plan. With node status, we definitely use imaging to understand the depth and compare the tumor spread and the lymph node burden. That’s a game changer in terms of how we deliver the radiation.
The real place we could go wrong is to undertreat something. It’s superficial in nature to give electron beam when that’s just the tip of the iceberg. As all of you know, it’s hard to salvage bad radiation. We must appropriately stage the patient up front to make sure we understand the full extent of their disease and target it to that person.
Glenn J. Hanna, MD: In reviewing this case and thinking about the discussion, this is someone who besides having a full skin exam would probably have MRI imaging that looks carefully at the nerves along the facial structure, the facial nerve, and back to the skull base, as well as the carotid. She would probably have a PET [positron emission tomography]–CT scalp to toe to understand whether there was micrometastatic involvement or any metastatic disease that was detectable given the size. There might even be a discussion with the outpatient psoriasis specialist: is there a plan for systemic immunologic agents in the future, and how would that impact systemic therapy decisions?
For this case, we jumped ahead and said that because of the location and some other factors, the patient was deemed not a good surgical candidate. In this case, we didn’t want to go down the road of palliative vs definitive radiation. The patient was started on a checkpoint inhibitor, a PD-1 inhibitor, cemiplimab, at standard flat dosing every 3 weeks.
I’ll turn to Dr Cohen and ask about using cemiplimab in this scenario for a patient who isn’t entertaining surgery or radiation or where that’s not a good option. I’ll leave you with these phase 2 study data to complement your thoughts.
Ezra Cohen, MD, FRCPSC, FASCO: Thanks, Glenn. This is perfect because the data speak for themselves. What we said about basal cell carcinoma applies to squamous cell carcinoma in the sense of tumor mutational burden. In fact, cutaneous squamous cell carcinomas have the highest mutational burden of any malignancy we’ve looked at. That forms the rationale for using immunotherapy and especially anti–PD-1 antibodies in this disease.
As we said in the last discussion, initially there were case reports—case series of activity—and that translated eventually into prospective phase 2 studies. This was the first 1: cemiplimab in a phase 2 trial in patients with advanced cutaneous squamous cell carcinoma. You can see these are longer follow-up data with a median follow-up of 15 months. These studies were started years ago. The study separated patients into 3 groups with different dosing formulations.
Without getting into the intricacies of all that, when we bring everything together, we clearly see these are active agents. Cemiplimab is active in this disease. Response rate is just short of 50%, but a little higher in patients with locally advanced disease. This patient may have a better efficacy profile than what we’re seeing. But look at the duration of response, and the estimated overall survival was 73%. The median duration of response, although it’s not seen here, is about 18 months. About half of these patients are going to benefit substantially. If you bring in the disease control rate, more than half are going to benefit from an agent like this. It’s a discussion worth having with a patient in this type of scenario.
This transcript has been edited for clarity.