Ann Hoeben, Hartgerink DEJ, Mosterd K, Postma AA, Lalisang R, Dinjens WNM, van den Hout MFCM, Speel EJM
Cutaneous Squamous Cell Carcinoma (cSCC) of the head and neck is etiologically associated with age, skin tone, UV light exposure, and also with medical conditions that cause immunosuppression. In most cases, patients with a primary cSCC of the head and neck can be cured by surgical excision and/or radiation therapy. However, in recurrent or advanced tumor stages curation with Radiotherapy (RT) or a surgical approach might be impossible. For these clinical settings, systemic treatment options are available. Palliative platin-based chemotherapy may be harmful to the elderly and/or immune-compromised cSCC patients with comorbidities. For this subgroup, biologicals that target for example the immune-suppressed microenvironment (e.g. the immune checkpoint inhibitors cemiplimab and pembrolizumab) or dysregulated tumorigenic pathways (e.g. the chimeric Immunoglobulin (Ig) G1 monoclonal antibody cetuximab that binds the extracellular domain of EGFR has shown to increase curation rates in unresectable, recurrent and/or metastasized cSCC (R/M cSCC) and is moving into the standard of care. Despite the fact that cetuximab has shown durable clinical responses in cSCC patients, the lack of biomarkers that predict cetuximab response and the unknown mechanisms of resistance are unmet medical needs. In this case report, we show that strong EGFR expression without an underlying EGFR gene mutation or amplification may be a sign of a favorable response to cetuximab treatment in cSCC. The presence of Microsatellite Instability (MSI) might have contributed to the favorable response, but may also be implicated in the final treatment resistance. Because both MSI and high PD-L1 expression were detected in this cSCC case, combined or sequential treatment of cetuximab with immune checkpoint inhibitors should be considered in cSCC management.