Concurrent radiation therapy with programmed cell death protein 1 inhibition leads to a complete response in advanced cutaneous squamous cell carcinoma

Abstract

Approximately 4 million cases of nonmelanoma skin cancer affecting 2.5 million individuals were diagnosed in the United States in 2012, with nearly half being cutaneous squamous cell carcinoma (CSCC).1 Risk factors for the development of CSCC include ultraviolet exposure, older age, and immunosuppression.2 There are no standard guidelines to manage advanced or recurrent CSCC. Various systems have been devised to predict which patients are at high risk of recurrence or metastasis, based on clinical or pathologic characteristics, including the American Joint Committee on Cancer and the Brigham and Women's Hospital staging systems. Management of these cases typically requires multidisciplinary care involving Mohs micrographic surgery, surgical oncology, medical oncology, and radiation oncology. The programmed cell death protein 1 (PD-1) receptor, found on the membranes of T cells, binds to the programmed death ligands 1 and 2 (PD-L1 and PD-L2), which are highly expressed in squamous cell cancers.3 The PD-1/PD-L1 interaction results in deactivation of T cells and thereby reduces anticancer immune surveillance. Increased PD-1 and PD-L1 expression levels have been associated with high-risk CSCC, perineural invasion, and organ transplant–associated CSCC compared with noncancerous skin specimens.4 A recent study examining the PD-1 inhibitor cemiplimab in unresectable and metastatic CSCC yielded response rates of 50% and 47%, respectively, with durable responses exceeding 6 months in more than 50% of patients.5 Subsequently, the US Food and Drug Administration approved cemiplimab for the treatment of unresectable and metastatic CSCC. Although PD-1 inhibition is now the standard of care for metastatic CSCC, its use in combination with other treatment modalities in the definitive setting is not yet well described. Here, we present the case of a patient with a diagnosis of locally advanced CSCC who showed complete response to concurrent radiation therapy and PD-1 inhibition.