Cemiplimab in Managing Advanced cSCC

Gregory A. Daniels, MD:Systemic therapies for unresectable or metastatic cutaneous squamous cell cancers have included in the past cytotoxic chemotherapies or epidermal growth factor receptor targeted therapy.

Recently, PD-1 [programmed cell death protein 1] blockade has come into play, and cemiplimab was approved last year as a therapy in unresectable locally advanced cutaneous squamous cell cancer, or metastatic cutaneous squamous cell cancer.

Cemiplimab was approved…after seeing data presented from 2 separate clinical run-ins—1 from a dose-finding study and 1 specifically in cutaneous squamous cell cancer. There, they reported response rates of approximately 50%. That’s been our experience, too, in this tumor type. The tumor type, perhaps being highly mutated, has a few characteristics about it, and that is a high response rate to these PD-1 blocking antibodies such as cemiplimab, as well as quick responses.

For example, I’ve had patients come in who had bleeding lesions, and maybe had a lot of pain. After 1 or 2 infusions, the patients are reporting back that they feel positive change for the lesions. It’s a little unusual for immune therapies where responses are often delayed. However, we’ve seen both a high rate of response as well as a quick response with cemiplimab.

Cemiplimab toxicities are similar to other agents in this class. Oncology is getting very familiar with PD-1 blockade, and we know that depending on the dose schedule as well as the combination with other agents. Cemiplimab is given as a single bolus infusion once every 3 weeks. With that kind of dosing as a single agent, I expect around 10% grade 3 or higher toxicities. The type of toxicities we usually see include fatigue, loose stools, and some rash, but generally, these are toxicities that are managed well by the patients and don’t require dose interruption. It’s that 10% of colitis, pneumonitis, or a rash that means we have to stop and intervene appropriately either with steroids or higher immune depression. We also have to be cognizant that those rare situations, such as neurologic toxicity or a cardiac toxicity, can happen.

Counseling patients on cemiplimab is similar to other PD-1 blocking antibodies. We personally will counsel the patients several times before administration of the drug. They’re given printed material on toxicities. They’re given website access for toxicities and numbers to call. They also are given cards to carry.

We sit down and discuss the basic mechanism of cemiplimab and PD-1 blockade, which leads to any kind of immune activation. Getting the patient to understand that mild things can happen, you definitely want to hear if there are any concerns, but those can usually be managed by themselves. But, anything they think is beyond mild, we want to know. Patients are heavily counseled and then followed up with during therapy.

For severe reactions to cemiplimab or PD-1 antibodies, what is almost always the first line of defense, besides just stopping the medication, are doses of steroids that can be as high as 1 or 2 mg per kilogram. For these toxicities, we use a grading system. For example, more than 6 stools a day is going to be a grade 3 toxicity, which triggers a response.

In the clinical trials, responses were outlined that are very similar to what the NCCN [National Comprehensive Cancer Network] recommends as far as immune-related adverse event management for any of these checkpoint inhibitors, and it can be effective if implemented according to the guidelines.

Transcript edited for clarity.

Case: A 79-Year-Old Male With Metastatic CSCC

April 2016

• A 79-year-old male presented to dermatologist with a large ulcerative lesion on clavicle; he reported lesion first appeared 5 months ago while living in Florida for the winter
• Diagnosed with localized cutaneous squamous cell carcinoma
• Standard surgical excision performed with 4 mm clinical margins; postoperative margins negative

May 2018

• Patient returns to dermatologist for follow-up c/o multiple lesions on shoulder and neck around the site of prior excision
• PE:
  • Multiple visible, ulcerated lesions, approximately 2-3cm in diameter; suspected tumor depth >5mm
  • Multiple palpable nodes ~2cm
• Imaging confirmed 7 mm invasion into subcutaneous fat; parotid nodal involvement
• Biopsy confirmed cutaneous squamous cell carcinoma, poorly-differentiated
• Diagnosis: Metastatic cutaneous squamous cell carcinoma
• Stage IV: T3N2M0
• Patient started on cemiplimab