Systemic Immunotherapy for Advanced Cutaneous Squamous Cell Carcinoma
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Advanced (i.e., unresectable) cutaneous squamous cell carcinoma (cSCC) is a rare condition with a dismal prognosis. Although less than 5% of cSCC patients develop metastases or local recurrence after complete excision, advanced cSCC is difficult to treat. These conditions tend to develop in elderly patients, although, at times, metastases are noted in middle-aged patients. Once metastasis occurs in cSCC, the 10-year survival rates fall to less than 20% for patients with regional lymph node involvement and less than 10% for patients with distant metastases, indicating that cSCC can be difficult to treat effectively when it is advanced. Traditionally, platinum-based therapy has been considered as a conventional option for advanced cSCC. It is efficacious to some degree, but the toxic effects of the combination treatments often prohibit their use in elderly patients. It has been a decade since the development of epidermal growth factor receptor (EGFR) inhibitors as agents that are less toxic. However, evidence regarding systemic therapy for advanced cSCC is limited because of a lack of high-quality prospective studies. Remarkably, the US Food and Drug Administration (FDA) approved an anti-PD-1 antibody treatment (cemiplimab) for the treatment of patients who are not candidates for curative surgery or curative radiation. It will be a promising treatment option for these types of rare conditions.
KeywordsSquamous cell carcinoma of the skin Chemotherapy Targeted therapy Immunotherapy Radiotherapy Metastasis Unresectable
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Conflict of Interest
Dai Ogata and Tetsuya Tsuchida declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 11.•• Migden MR, Rischin D, Schmults CD, Hauschild A, Lewis KD, Chung CH, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379(4):341–51 This article is the first cemiplimab, an anti-PD-L1 antibody, prospective trial in patients with advanced cSCC for evaluating efficacy and safety. It indicates anti-PD-L1 antibody therapy significantly improves the prognosis of advanced cSCC patients.CrossRefGoogle Scholar
- 17.Freeman A, Bridge JA, Maruthayanar P, Overgaard NH, Jung JW, Simpson F, et al. Comparative immune phenotypic analysis of cutaneous squamous cell carcinoma and intraepidermal carcinoma in immune-competent individuals: proportional representation of CD8þ T-cells but not FoxP3þ regulatory T-cells is associated with disease stage. PLoS One. 2014;9:e110928.CrossRefGoogle Scholar
- 21.FDA. FDA approves first treatment for advanced form of the second most common skin cancer. 2018. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm622044.htm. Accessed 2 Jan 2019.
- 33.Merck & Co., Inc. Prescribing information: KEYTRUDA (pembrolizumab) injection, for intravenous use. 2017. https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf. Accessed 2 Jan 2019.
- 34.Bristol-Myers Squibb Company. Prescribing information: OPDIVO (nivolumab) injection, for intravenous use. 2017. https://packageinserts.bms.com/pi/pi_opdivo.pdf. Accessed 2 Jan 2019.
- 35.•• Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–67 This article describes randomized, open-label, phase 3 trial with recurrent squamous-cell carcinoma of the head and neck and nivolumab prolonged survival, as compared with standard therapy.CrossRefGoogle Scholar
- 36.• LQM C, Haddad R, Gupta S, Mahipal A, Mehra R, Tahara M, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: Results from the phase Ib KEYNOTE-012 Expansion Cohort. J Clin Oncol. 2016;34(32):3838–45 This article describes a phase Ib, multicenter, nonrandomized, multicohort study of pembrolizumab in patients with advanced solid tumors.CrossRefGoogle Scholar
- 37.• Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016;17(7):956–65 This article describes an open-label, multicenter, phase 1b trial of patients with recurrent or metastatic squamous cell carcinoma of the head and neck.CrossRefGoogle Scholar