Immune Checkpoint Inhibitors for Treating Advanced Cutaneous Squamous Cell Carcinoma
Cutaneous squamous cell carcinoma (CSCC) is one of the most common human malignancies, and the incidence is increasing with time. High mutational loads, known infiltration with lymphocytes, and programmed death (PD)-ligand 1 (PD-L1) expression suggest that immune checkpoint inhibitors, such as PD-1 inhibitors, may show utility in treating CSCC, similar to response see in other solid tumor types. Recently, the robust responsiveness of CSCCs to the PD-1 inhibitor cemiplimab was revealed in the results of a combined phase I/II clinical trial, with an overall response rate of 50% and a durable response exceeding 6 months in 57% of responders. Compared to prior systemic therapies with scant data for efficacy and safety, cemiplimab is a breakthrough therapy, the first systemic drug approved for advanced CSCCs. Other immune checkpoint inhibitors have shown promise through case reports and series, and are currently in clinical development for CSCCs.
Compliance with Ethical Standards
No external funding was used in the preparation of this manuscript.
Conflict of interest
Anne Lynn S. Chang has received research grants from Regeneron and Merck, and was an advisory board member for Regeneron and Merck. Roma Patel declares that she has no conflicts of interest that might be relevant to the contents of this article.
- 11.Amoils M, Kim J, Kee C, Sunwoo JB, Colevas AD, Aasi SZ, et al. PD-L1 expression and tumor-infiltrating lymphocytes in high risk and metastatic cutaneous squamous cell carcinoma. Otolaryngol Head Neck Surg. https://doi.org/10.1177/0194599818788057.
- 16.Garcia-Pedrero J, Martinez-Camblor P, Diaz-Coto S, Munguia-Calzada P, Vallina-Alvarez A, Vazquez-Lopez F, et al. Tumor programmed cell death ligand 1 expression correlates with nodal metastasis in patients with cutaneous squamous cell carcinoma of the head and neck. J Am Acad Dermatol. 2017;77(3):527–33.CrossRefGoogle Scholar
- 18.Borradori L, Sutton B, Shayesteh P, Daniels G. Rescue therapy with anti-programmed cell death protein 1 inhibitors of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: preliminary experience in five cases. Br J Dermatol. 2016;175(6):1382–6. https://doi.org/10.1111/bjd.14642.CrossRefGoogle Scholar
- 20.Blum V, Muller B, Hofer S, Pardo E, Zeidler K, Diebold J, et al. Nivolumab for recurrent cutaneous squamous cell carcinoma: three cases. Eur J Dermatol. 2018;28(1):78–91.Google Scholar
- 21.Deinlein T, Lax SF, Schwarz T, Giuffrida R, Schmid-Zalaudek K, Zalaudek I. Rapid response of metastatic cutaneous squamous cell carcinoma to pembrolizumab in a patient with xeroderma pigmentosum: case report and review of the literature. Eur J Cancer. 2017;83:99–102. https://doi.org/10.1016/j.ejca.2017.06.022.CrossRefGoogle Scholar
- 23.Hauschild A, Eichstaedt J, Möbus L, Kähler K, Weichenthal M, Schwarz T, et al. Regression of melanoma metastases and multiple non-melanoma skin cancers in xeroderma pigmentosum by the PD1-antibody pembrolizumab. Eur J Cancer. 2017;77:84–7. https://doi.org/10.1016/j.ejca.2017.02.026.CrossRefGoogle Scholar
- 24.Miller DM, Faulkner-Jones BE, Stone JR, Drews RE. Complete pathologic response of metastatic cutaneous squamous cell carcinoma and allograft rejection after treatment with combination immune checkpoint blockade. J Am Acad Dermatol. 2017;3:412–5.Google Scholar
- 27.Merck Sharp and Dohme Corp (2018) A phase 2, open-label, single arm study to evaluate the safety and efficacy of pembrolizumab in participants with recurrent or metastatic cutaneous squamous cell carcinoma (R/M cSCC) [ClinicalTrials.gov identifier NCT03284424]. National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov. Accessed 10 Nov 2018.
- 28.Regeneron Pharmaceuticals (2018) A phase 2 study of REGN2810, a fully human monoclonal antibody to programmed death-1 (PD-1) in patients with advanced cutaneous squamous cell carcinoma [ClinicalTrials.gov identifier NCT02760498]. National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov. Accessed 10 Nov 2018.
- 29.CureVac AG (2018) Phase I study of intratumoral CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma [ClinicalTrials.gov identifier NCT02760498]. National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov. Accessed 10 Nov 2018.