Immunotherapy in Squamous Cell Skin Carcinoma: A Game Changer?

Abstract

A 74-year-old white male was diagnosed with squamous cell carcinoma in 2013. Six months after Mohs surgery, he underwent a left superficial parotidectomy, left neck dissection, and excision of the left postauricular lymph node after confirmation of lymphatic spread. Pathology from the left parietal scalp lesion revealed multifocal invasive squamous cell carcinoma. Extranodal tumor extension was noted in a postauricular lymph node and left parotid gland, and he was diagnosed with stage IV squamous cell carcinoma.Despite receiving adjuvant radiation therapy from December 2013 to March 2014 to the right neck and scalp, a skin graft after 5 months was confirmed to have squamous cell carcinoma. Positron emission tomography-computed tomography showed metastatic disease at the level of cricoarytenoid cartilage and bilateral parotid glands. Cetuximab was discontinued, as he had an anaphylaxis episode after the first dose, and he later underwent localized radiation to his left temple.He returned after a year with multiple cutaneous nodular masses over the left face and neck, with a large ulcerated necrotic area over the left temporal region (Figure). Due to the lack of further chemotherapy options, he was started on pembrolizumab.Anti-programmed death ligand 1 testing from the tumor showed a staining distribution of 1%-24% and a staining intensity of 1þ, with a low positive result. Next-generation sequencing assay showed genomic alterations in AKT3 E17K,

Clinical Remission of Cutaneous Squamous Cell Carcinoma of the Auricle with Cetuximab and Nivolumab

“…Recently, reports of six patients have demonstrated tumor regression of treatment-refractory cutaneous SCC specifically affecting the pre- and post-auricular and temporal regions with nivolumab as well as pembrolizumab, another PD-1 antibody [ 15 , 16 , 17 , 18 , 19 ]. Similar to nivolumab, pembrolizumab exerts its effect by interrupting the pathway that disarms T lymphocytes, preventing the immune-mediated destruction of tumor cells.…”

“…Similar to nivolumab, pembrolizumab exerts its effect by interrupting the pathway that disarms T lymphocytes, preventing the immune-mediated destruction of tumor cells. Review of the literature revealed 12 cases of locally advanced or metastatic SCC treated with nivolumab or pembrolizumab [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. An ongoing clinical trial (NCT02964559) is examining pembrolizumab as a primary treatment for locally advanced or metastatic SCC of the skin [ 23 ].…”

Perineural Invasion and Perineural Tumor Spread in Head and Neck Cancer

“…108 A number of series have documented the efficacy of checkpoint inhibition for recurrent and metastatic cutaneous SCC, and one trial reported a response rate of approximately 50%. 106,[109][110][111] Numerous trials are underway to clarify the role of immunotherapy in the management of cutaneous SCC postoperatively and in the recurrent and metastatic settings. Case reports of the safety of hedgehog inhibitors with radiation for BCC have also been reported, and 2 such compounds are approved by the U.S. Food and Drug Administration for use in BCC that cannot be treated definitively.…”

Pattern of response of unresectable and metastatic cutaneous squamous cell carcinoma to programmed death‐1 inhibitors: A review of the literature

“…Recommended doses are 3 mg for kilograms of weight every 3 weeks as intravenous (iv) infusion for a period of 30 minutes. Among the different PD-1 inhibitors, the number of patients treated is the widest, about 28 reported in the literature (Assam et al, 2016;Borradori et al, 2016;Chang et al, 2016;Degache et al, 2018;Deinlein et al, 2017;Ferrarotto, 2017;Lipson et al, 2016;Ravulapati et al, 2017;Stevenson et al, 2017;Tran et al, 2017;Winkler et al, 2017;Zalaudek et al, 2019), excluding the ongoing trials in Phase I and II (Licitra et al, 2017;Kudchadkar et al, 2018;Maubec et al, 2019). Although the larger number of reported cases, responses data are not enough and in addition with short period of follow-up.…”