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Systemic treatment of patients with advanced cutaneous squamous cell carcinoma: response rates and outcomes of the regimes used

Published:January 28, 2020DOI:https://doi.org/10.1016/j.ejca.2019.12.018

      Highlights

      • There are limited prospective studies on systemic therapy for advanced cutaneous squamous cell carcinoma.
      • Cisplatin-based chemotherapy is not always superior to other drugs.
      • RCT improves overall survival in patients with nodal squamous cell carcinoma.

      Abstract

      Background

      Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer. Few patients with cSCC experience metastases, but the prognosis of advanced cSCC (acSCC) is dismal. Evidence regarding systemic therapy for acSCC is limited. Therefore, we aimed to determine the most effective systemic treatment for acSCC.

      Patients and methods

      This retrospective study involved 16 Japanese institutions. We documented patient and tumour characteristics and disease course of patients with acSCC who received systemic therapy between 1st January 2006 and 31st December 2015. We compared the overall survival (OS) and progression-free survival (PFS) for (1) platinum versus non-platinum groups, (2) radiation plus chemotherapy first-line therapy (RCT) versus non-RCT groups and (3) platinum-based RCT versus non–platinum-based RCT groups.

      Results

      Although the use of platinum-based systemic therapy was not associated with statistically significant improvements in PFS and OS, there were significant differences between the RCT and non-RCT groups (PFS: p < 0.001, OS: p = 0.003). In the subgroup analysis, RCT significantly prolonged PFS and OS in the nodal SCC (nSCC) group. For the RCT and non-RCT groups, the median OS was 110 and 14 months, respectively, and the 5-year OS rate was 54% and 21%, respectively.

      Conclusion

      RCT could improve OS in patients with nSCC. However, further multicenter prospective studies are needed to establish evidence for superiority of RCT.

      Keywords

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      References

        • Amini S.
        • Viera M.H.
        • Valins W.
        • Berman B.
        Nonsurgical innovations in the treatment of nonmelanoma skin cancer.
        J Clin Aesthetic Dermatol. 2010; 6: 20-34
        • Rogers H.W.
        • Weinstock M.A.
        • Harris A.R.
        • Hinckley M.R.
        • Feldman S.R.
        • Fleischer A.B.
        • et al.
        Incidence estimate of nonmelanoma skin cancer in the United States, 2006.
        Arch Dermatol. 2010; 3: 283-287
        • Ferlay J.
        • Ervik M.
        • Lam F.
        • Colombet M.
        • Mery L.
        • Piñeros M.
        • et al.
        Global cancer observatory: cancer today.
        International Agency for Research on Cancer, Lyon, France2018 (Available from:)
        • Ishihara K.
        • Saida T.
        • Otsuka F.
        • Yamazaki N.
        Statistical profiles of malignant melanoma and other skin cancers in Japan: 2007 update.
        Int J Clin Oncol. 2008; 13: 33-41
        • Martinez J.C.
        • Cook J.L.
        High-risk cutaneous squamous cell carcinoma without palpable lymphadenopathy: is there a therapeutic role for elective neck dissection?.
        Dermatol Surg. 2007; 33: 410-420
        • Brantsch K.D.
        • 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
        • Schmults C.D.
        • Karia P.S.
        • Carter J.B.
        • Han J.
        • Qureshi A.A.
        Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study.
        JAMA Dermatol. 2013; 149: 541-547
        • Alam M.
        • Ratner D.
        Cutaneous squamous-cell carcinoma.
        N Engl J Med. 2001; 344: 975e83
        • 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: 34e43
        • Fujisawa Y.
        • Funakoshi T.
        • Nakamura Y.
        • Ishii M.
        • Asai J.
        • Shimauchi T.
        • et al.
        Nation-wide survey of advanced non-melanoma skin cancers treated at dermatology departments in Japan.
        J Dermatol Sci. 2018; 92: 230-236
        • Guthrie Jr., T.H.
        • Porubsky E.S.
        • Luxenberg M.N.
        • Shah K.J.
        • Wurtz K.L.
        • Watson P.R.
        • et al.
        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
        • Khansur T.
        • Kennedy A.
        Cisplatin and 5-fluorouracil for advanced locoregional and metastatic squamous cell carcinoma of the skin.
        Cancer. 1991; 67: 2030-2032
        • Ikegawa S.
        • Saida T.
        • Obayashi H.
        • Sasaki A.
        • Esumi H.
        • Ikeda S.
        • et al.
        Cisplatin combination chemotherapy in squamous cell carcinoma and adenoid cystic carcinoma of the skin.
        J Dermatol. 1989; 16: 227-230
        • Nakamura K.
        • Okuyama R.
        • Saida T.
        • Uhara H.
        Platinum and anthracycline therapy for advanced cutaneous squamous cell carcinoma.
        Int J Clin Oncol. 2013; 18: 506-509
        • Lewis C.M.
        • Glisson B.S.
        • Feng L.
        • Wan F.
        • Tang X.
        • Wistuba I.I.
        • et al.
        A phase II study of gefitinib for aggressive cutaneous squamous cell carcinoma of the head and neck.
        Clin Cancer Res. 2012; 18: 1435-1446
        • 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
        • FDA
        FDA approves first treatment for advanced form of the second most common skin cancer.
        2018
        • Migden M.R.
        • Rischin D.
        • Schmults C.D.
        • Guminski A.
        • Hauschild A.
        • Lewis K.D.
        • et al.
        PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma.
        N Engl J Med. 2018; 379: 341-351
        • Oken M.
        • Creech R.H.
        • Tormey D.C.
        • Horton J.
        • Davies T.E.
        • McFadden E.T.
        • et al.
        Toxicity and response criteria of the Eastern Cooperative Oncology Group.
        Am J Clin Oncol. 1982; 5: 649-655
        • Edge S.
        • Byrd D.R.
        • Compton C.C.
        • Fritz A.G.
        • Greene F.L.
        • Trotti A.
        AJCC cancer staging manual.
        7th ed. Springer, New York2010
        • Eisenhauer E.A.
        • Therasse P.
        • Bogaerts J.
        • Schwartz L.H.
        • Sargent D.
        • Ford R.
        • et al.
        New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).
        Eur J Cancer. 2009 Jan; 45: 228-247
      1. National Cancer Institute’s Common Terminology Criteria for Adverse EventsAEs ([AE] version 4.03). Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_40 [Accessed 01 March 2019].

        • Kanda Y.
        Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics.
        Bone Marrow Transplant. 2013; 48: 452-458
        • Karia P.S.
        • Han J.
        • Schmults C.D.
        Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012.
        J Am Acad Dermatol. 2013; 68: 957e66
        • Venables Z.C.
        • Autier P.
        • Nijsten T.
        • Wong K.F.
        • Langan S.M.
        • Rous B.
        • et al.
        Nationwide incidence of metastatic cutaneous squamous cell carcinoma in England.
        JAMA Dermatol. 2019 Mar 1; 155: 298-306
        • Ishii Y.
        • Sakaino M.
        • Watanabe S.
        • Kubo N.
        • Onisama S.
        • Maruyama H.
        • et al.
        Nationwide survey of squamous cell carcinoma and Bowen’s disease.
        Skin Cancer Japn. 2013; 2: 195-204
        • Daya M.
        • Balakrishan T.
        Advanced Marjolin's ulcer of the scalp in a 13-year-old boy treated by excision and free tissue transfer: case report and review of literature.
        Indian J Plast Surg. 2009 Jan-Jun; 42: 106-111
        • UNAIDS data
      2. Global observatory on donation and transplantation. Accessed 28 May 2019. http://www.transplant-observatory.org/data-charts-and-tables/.

        • Jarkowski III, A.
        • Hare R.
        • Loud P.
        • Skitzki J.J.
        • Kane III, J.M.
        • May K.S.
        • 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
        • Teramoto Y.
        • Nakamura Y.
        • Yamada K.
        • Yamamoto A.
        Oral S-1 in advanced cutaneous squamous cell carcinoma.
        J Dermatol. 2014 Jun; 41: 494-497
        • Dhruva N.
        • Ardeshirpour F.
        • Tepper J.E.
        • Shores C.G.
        • Rosenman J.G.
        • Shockley W.W.
        • et al.
        Concomitant radiotherapy and chemotherapy for high-risk nonmelanoma skin carcinomas of the head and neck.
        Int J Surg Oncol. 2011; 2011
        • Porceddu S.V.
        • Bressel M.
        • Poulsen M.G.
        • Stoneley A.
        • Veness M.J.
        • Kenny L.M.
        • et al.
        Postoperative concurrent chemoradiotherapy versus postoperative radiotherapy in high-risk cutaneous squamous cell carcinoma of the head and neck: the randomized phase III TROG 05.01 trial.
        J Clin Oncol. 2018; 36: 1275-1283
        • Lu S.M.
        • Lien W.W.
        Concurrent radiotherapy with cetuximab or platinum-based chemotherapy for locally advanced cutaneous squamous cell carcinoma of the head and neck.
        Am J Clin Oncol. 2018; 41: 95-99
        • Hiura A.
        • Yoshino K.
        • Maeda T.
        • Nagai K.
        • Oaku S.
        • Kato M.
        • et al.
        Chemoradiotherapy could improve overall survival of patients with stage IV cutaneous squamous cell carcinoma: analysis of 34 cases.
        Br J Dermatol. 2019 Jun; 180: 1557-1558
        • Ogata D.
        • Tsuchida T.
        Systemic immunotherapy for advanced cutaneous squamous cell carcinoma.
        Curr Treat Options Oncol. 2019; 20: 30