Efficacy of a programmed death-1 checkpoint inhibitor in a case of cutaneous squamous cell carcinoma harboring mutations of TP53 and BRCA2.

Immune checkpoint blockades were reported to result in clinical responses in inoperable and metastatic cutaneous squamous cell carcinoma (cSCC). This report describes an 87-year-old woman with recurrent cSCC that was initially responsive to cetuximab (the monoclonal antibody against epithelial growth factor receptor) but eventually became refractory to cetuximab and multiple subsequent salvage chemotherapy regimens. Next-generation sequencing of the tumor discovered three single-nucleotide mutations in TP53, copy number amplification in Src, and a heterozygous deletion in BRCA2. Because of the high mutation burden of her neoplasm (35.2 mutations per megabase), we treated her with a programmed death-1 (PD-1) checkpoint inhibitor, pembrolizumab, for 10 months. The tumor regressed 3 months later and complete pathological remission was achieved 10 months after starting treatment. As of writing, the patient has been disease free for 17 months after discontinuing treatment. This is the first reported case of heterozygous deletion of BRCA2 in cSCC. The high mutation burden and BRCA2 mutation might explain why this tumor was highly sensitive to anti-PD-1 treatment.