Treatment Options for Advanced Cutaneous Squamous Cell Carcinoma After Cemiplimab Progression

Primary Treatment Considerations

The National Comprehensive Cancer Network recommends cetuximab, an EGFR inhibitor, for locally or regionally advanced cutaneous squamous cell carcinoma of the head and neck, particularly in combination with radiation therapy or chemotherapy 1
EGFR inhibitors have demonstrated efficacy in metastatic cutaneous SCC, albeit based on limited data, and may provide benefit after immunotherapy failure 2
The American Academy of Dermatology suggests that EGFR inhibitors represent a mechanistically distinct approach from checkpoint inhibition 2

The National Comprehensive Cancer Network recommends regional lymph node dissection as the preferred treatment if nodal disease is present and surgically resectable, even after systemic therapy failure 3, 1
Complete surgical excision should be reconsidered if disease has become technically resectable, as incomplete excision is associated with poor prognosis 1

Cisplatin as a single agent or in combination therapy may be considered for metastatic disease, though data are limited 2
The National Comprehensive Cancer Network suggests that combination chemoradiation therapy should be considered for inoperable disease, particularly with concurrent cisplatin 4, 3

The American Academy of Dermatology recommends that patients with advanced disease should be provided with or referred for best supportive and palliative care to optimize symptom management and maximize quality of life 2
The Journal of Thoracic Oncology suggests that for patients with performance status 3-4, palliative care/best supportive care is recommended over aggressive systemic therapy 5, 6, 7

The National Comprehensive Cancer Network notes that despite resection followed by radiation therapy, high-risk patients experience locoregional recurrence rates of 30%, distant metastasis rates of 25%, and 5-year survival rates of only 40% 3
Praxis Medical Insights recommends multidisciplinary consultation for patients with locoregional or distant metastases, particularly in immunosuppressed individuals who have 2- to 3-fold increased risk of metastasis 1