Cutaneous Squamous Cell Carcinoma

The Disease

Cutaneous squamous cell carcinoma (cSCC), is the second most common form of non-melanoma skin cancer (NMSC) comprising around 20% of all NMSC in the United States, with over 200,000 new cases each year. The majority of cSCC can be effectively treated with surgical excision however there is a high-risk cutaneous squamous cell carcinoma subgroup with an estimated 8,000 cases of nodal metastasis and 3,000 deaths in the United States annually, attributable to this subset which has substantially higher rates of recurrence and metastases.

Current Management

Surgery and targeted radiation are major first line treatment options for cutaneous SCC however recurrence frequently occurs within a prior radiation field and further radiotherapy is not an option. In addition, palliative surgery is generally associated with morbidity without improving survival. Treatment after failure of surgery and radiation therapy generally involves chemotherapy but these options tend to have limited durability and can be associated with significant toxicities. Cetuximab, an EGFR inhibitor is used for metastatic and recurrent skin cancers but disease often recurs within 6-8 months. Combined treatment regimes, such as chemoradiotherapy can improve prognosis but response rates remain very low. Cemiplimab, an antibody targeting PD-1 has been reported to have a 47% overall response rates for patients with advanced Cutaneous SCC (4% complete and 44% partial response rates) and 61% of subjects reported to have median response duration 6 months or longer.

The Clinical Need

Clinical management is predominantly palliative focused on symptom relief. Cetuximab or platinum-based chemotherapy can have significant toxicity especially in older patients. Cemiplimab offers more durable and better tolerated responses in patients that respond to that treatment however there is still an important need for effective local regional therapy for the patients that do not respond or fail these treatment options.