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In patients with localized <jats:styled-content style=\"fixed-case\">cSCC<\/jats:styled-content>, complete surgical resection is indicated. Radiotherapy should be performed in patients with non\u2010resectable tumours or in patients who are not suitable for surgery. Systemic therapy is reserved for <jats:styled-content style=\"fixed-case\">cSCC<\/jats:styled-content> that are neither surgically nor radiotherapeutically curable due to their extensive local spread and\/or local or distant metastasis. In the absence of prospective randomized phase 3 trials to evaluate and compare the efficacy and safety of chemotherapeutics, epidermal growth factor receptor (<jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>) inhibitors and anti\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 antibodies, no final recommendation for systemic therapy can be given for patients with locally advanced or metastatic <jats:styled-content style=\"fixed-case\">cSCC<\/jats:styled-content>. Anti\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 antibodies currently show promising results with response rates of up to 50% in both locally advanced and metastatic <jats:styled-content style=\"fixed-case\">cSCC<\/jats:styled-content>. Anti\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 antibodies appear to achieve higher response rates compared with <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> inhibitors, and the duration of response appears to be superior to both chemotherapy and <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> inhibitors. Compared with chemotherapy, the side effect profile of anti\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 antibodies appears to be favourable. Altogether, <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 inhibitors are expected to become the new standard of care for patients with locally advanced and metastatic <jats:styled-content style=\"fixed-case\">cSCC<\/jats:styled-content>. Currently, placebo\u2010controlled clinical trials are investigating the adjuvant use of cemiplimab and pembrolizumab in patients undergoing resection and radiotherapy of high\u2010risk <jats:styled-content style=\"fixed-case\">cSCC<\/jats:styled-content>. Patients not eligible for anti\u2010<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 treatment, e.g. in organ transplant recipients, or in patients refractory to anti<jats:italic>\u2010<\/jats:italic><jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content><jats:italic>\u2010<\/jats:italic>1 may be offered <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> inhibitors and\/or chemotherapies. Chemotherapies appear to be superior to <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> inhibitors in terms of response rates, whereas <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> inhibitors have a more favourable toxicity profile. <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> inhibitors are therefore more suitable for multimorbid and\/or frail elderly patients. By combining <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> inhibitors with local therapy such as surgery or radiotherapy, response rates and duration of response may be improved.<\/jats:p>","DOI":"10.1111\/jdv.16024","type":"journal-article","created":{"date-parts":[[2019,12,13]],"date-time":"2019-12-13T10:23:39Z","timestamp":1576232619000},"page":"38-43","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Medical treatment of advanced cutaneous squamous\u2010cell carcinoma"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2164-4644","authenticated-orcid":false,"given":"F.F.","family":"Gellrich","sequence":"first","affiliation":[{"name":"Dermatology National Center for Tumor Diseases University Hospital Carl Gustav Carus Dresden 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