Real-world Treatment Patterns and Outcomes with Systemic Therapies in Unresectable Locally Advanced and Metastatic Cutaneous Squamous Cell Carcinoma in Germany
Keywords:advanced squamous cell carcinoma, chemotherapy, EGFR-inhibition
Advanced cutaneous squamous cell carcinoma is a challenge to treat. Conventional systemic treatment options include chemotherapy and epidermal growth factor receptor-inhibitors. The aim of this study was to assess clinical outcomes with systemic treatments in advanced cutaneous squamous cell carcinoma. Patients receiving systemic treatment at the Tübingen Dermato-Oncology centre between 2007 and 2017 were identified (n = 59). Median age was 76 years (interquartile range (IQR) 71–80 years), 83.1% of patients were male, 72.9% had metastatic cutaneous squamous cell carcinoma, and 27.1% had unresectable locally advanced cutaneous squamous cell carcinoma. During median follow-up of 52 weeks (IQR 27–97 weeks), overall response rate was 14.3%, and disease control rate was 53.6%. Median progression-free survival was 15 weeks (IQR 8–42 weeks), and median overall survival was 52 weeks (IQR 27–97 weeks). Patients receiving chemoradiation vs chemotherapy alone showed better overall survival (hazard ratio 0.41, p = 0.014,) and progression-free survival (hazard ratio 0.42, p = 0.009); no differences were observed for metastatic cutaneous squamous cell carcinoma vs locally advanced cutaneous squamous cell carcinoma patients. Although chemotherapy and/or cetuximab showed limited outcomes in advanced cutaneous squamous cell carcinoma, such therapy may still be an option when anti-PD-1 treatment is contraindicated.
Leiter U, Eigentler T, Garbe C. Epidemiology of skin cancer. Adv Exp Med Biol 2014; 810: 120-140.
Leiter U, Keim U, Eigentler T, Katalinic A, Holleczek B, Martus P, et al. Incidence, mortality, and trends of nonmelanoma skin cancer in Germany. J Invest Dermatol 2017; 137: 1860-1867.
Katalinic A, Kunze U, Schäfer T. Epidemiology of cutaneous melanoma and non-melanoma skin cancer in Schleswig-Holstein, Germany: incidence, clinical subtypes, tumour stages and localization (epidemiology of skin cancer). Br J Dermatol 2003; 149: 1200-1206.
Heppt MV, Leiter U, Steeb T, Amaral T, Bauer A, Becker JC, et al. S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma - short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators. J Dtsch Dermatol Ges 2020; 18: 275-294.
Brantsch KD, Meisner C, Schönfisch B, Trilling B, Wehner-Caroli J, Röcken M, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol 2008; 9: 713-720.
Amaral T, Osewold M, Presser D, Meiwes A, Garbe C, Leiter U. Advanced cutaneous squamous cell carcinoma: real world data of patient profiles and treatment patterns. J Eur Acad Dermatol Venereol 2019; 33: 44-51.
Hillen U, Leiter U, Haase S, Kaufmann R, Becker J, Gutzmer R, et al. Advanced cutaneous squamous cell carcinoma: a retrospective analysis of patient profiles and treatment patterns - results of a non-interventional study of the DeCOG. Eur J Cancer 2018; 96: 34-43.
Maubec E, Petrow P, Scheer-Senyarich I, Duvillard P, Lacroix L, Gelly J, et al. Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin. J Clin Oncol 2011; 29: 3419-3426.
Khansur T, Kennedy A. Cisplatin and 5-fluorouracil for advanced locoregional and metastatic squamous cell carcinoma of the skin. Cancer 1991; 67: 2030-2032.
Cartei G, Cartei F, Interlandi G, Meneghini G, Jop A, Zingone G, et al. Oral 5-fluorouracil in squamous cell carcinoma of the skin in the aged. Am J Clin Oncol 2000; 23: 181-184.
Migden MR, Khushalani NI, Chang ALS, Lewis KD, Schmults CD, Hernandez-Aya L, et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol 2020; 21: 294-305.
Grob JJ, Gonzalez R, Basset-Seguin N, Vornicova O, Schachter J, Joshi A, et al. Pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma: a single-arm Phase II trial (KEYNOTE-629). J Clin Oncol 2020; 38: 2916-2925.
Stratigos AJ, Garbe C, Dessinioti C, Lebbe C, Bataille V, Bastholt L, et al. European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 2. Treatment. Eur J Cancer 2020; 128: 83-102.
Cowey CL, Robert NJ, Espirito JL, Davies K, Frytak J, Lowy I, et al. Clinical outcomes among unresectable, locally advanced, and metastatic cutaneous squamous cell carcinoma patients treated with systemic therapy. Cancer Med 2020; 9: 7381-7387.
Jarkowski A, 3rd, Hare R, Loud P, Skitzki JJ, Kane JM, 3rd, May KS, et al. Systemic therapy in advanced cutaneous squamous cell carcinoma (CSCC): The Roswell Park Experience and a review of the literature. Am J Clin Oncol 2016; 39: 545-548.
Chapalain M, Baroudjian B, Dupont A, Lhote R, Lambert J, Bagot M, et al. Stage IV cutaneous squamous cell carcinoma: treatment outcomes in a series of 42 patients. J Eur Acad Dermatol Venereol 2020; 34: 1202-1209.
Schmitt J, Seidler A, Diepgen TL, Bauer A. Occupational ultraviolet light exposure increases the risk for the development of cutaneous squamous cell carcinoma: a systematic review and meta-analysis. Br J Dermatol 2011; 164: 291-307.
Kumar M, Nanavati R, Modi TG, Dobariya C. Oral cancer: etiology and risk factors: a review. J Cancer Res Ther 2016; 12: 458-463.
Salzmann M, Leiter U, Loquai C, Zimmer L, Ugurel S, Gutzmer R, et al. Programmed cell death protein 1 inhibitors in advanced cutaneous squamous cell carcinoma: real-world data of a retrospective, multicenter study. Eur J Cancer 2020; 138: 125-132.
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: 956-965.
Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med 2018; 379: 341-351.
Bonomo P, Loi M, Desideri I, Olmetto E, Delli Paoli C, Terziani F, et al. Incidence of skin toxicity in squamous cell carcinoma of the head and neck treated with radiotherapy and cetuximab: a systematic review. Crit Rev Oncol Hematol 2017; 120: 98-110.
Montaudié H, Viotti J, Combemale P, Dutriaux C, Dupin N, Robert C, et al. Cetuximab is efficient and safe in patients with advanced cutaneous squamous cell carcinoma: a retrospective, multicentre study. Oncotarget 2020; 11: 378-385.
Gold KA, Kies MS, William WN, Jr, Johnson FM, Lee JJ, Glisson BS. Erlotinib in the treatment of recurrent or metastatic cutaneous squamous cell carcinoma: a single-arm phase 2 clinical trial. Cancer 2018; 124: 2169-2173.
Nottage MK, Lin C, Hughes BG, Kenny L, Smith DD, Houston K, et al. Prospective study of definitive chemoradiation in locally or regionally advanced squamous cell carcinoma of the skin. Head Neck 2017; 39: 679-683.
Guthrie TH, Jr, Porubsky ES, Luxenberg MN, Shah KJ, Wurtz KL, Watson PR. Cisplatin-based chemotherapy in advanced basal and squamous cell carcinomas of the skin: results in 28 patients including 13 patients receiving multimodality therapy. J Clin Oncol 1990; 8: 342-346.
Sadek H, Azli N, Wendling JL, Cvitkovic E, Rahal M, Mamelle G, et al. Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin. Cancer 1990; 66: 1692-1696.
How to Cite
Copyright (c) 2021 Felix Kramb, Christoph Doerfer, Andreas Meiwes, Karthik Ramakrishnan, Thomas Eigentler, Claus Garbe, Ulrike Keim, Ulrike Leiter
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.