Molecular Profile of Advanced Cutaneous Squamous Cell Carcinoma

BACKGROUND: Patients with advanced cutaneous squamous cell carcinoma (cSCC) frequently have high tumor mutation burdens (TMBs) but cannot tolerate immunotherapy due to comorbid conditions or already immunosuppressed states. OBJECTIVE: We considered whether these patients might be good candidates for targeted therapy if unique genetic mutations are identified. METHODS: Biopsies of primary tumors or metastases of advanced cSCC from seven patients were sent for FoundationOne testing. Genomic alterations and TMBs were compiled from these samples and used to tailor therapy when possible. Patients were followed for changes in their disease burden. RESULTS: Eight biopsies taken from seven patients were sent for FoundationOne testing. Sixty-three genomic alterations were identified. Thirteen genes had mutations occur more than once, with mutations in TP53 being the most frequently identified (100% of patients). In one patient, an ERBB3 mutation was identified, and lapatinib was added to nivolumab for a six-month course of treatment, after which point the patient experienced stabilization of disease without progression for two years as of the most recent follow-up. CONCLUSION: More routine investigation of cSCC tumors with next-generation sequencing can help to identify unique mutations that respond favorably to targeted therapy in these notoriously difficult-to-treat malignancies.