Cutaneous squamous cell carcinoma

Section editor
	Elizabeth Buchbinder, MD Dana-Farber Cancer Institute Boston, MA LinkedIn

6 regimens on this page 9 variants on this page

Guidelines

NCCN

• NCCN Guidelines - Squamous Cell Skin Cancer

Neoadjuvant chemotherapy

Bleomycin & Cisplatin

Regimen

Study	Evidence
Denic 1999	Pilot, <20 patients reported

Chemotherapy

• Cisplatin (Platinol) 20 mg/m² IV once per day on days 1 to 4
• Bleomycin (Blenoxane) 20 mg IV once per day on days 1 to 4

21-day cycle for 3 cycles

Subsequent treatment

• Surgery

References

1. Denic S. Preoperative treatment of advanced skin carcinoma with cisplatin and bleomycin. Am J Clin Oncol. 1999 Feb;22(1):32-4. link to original article contains protocol PubMed

Adjuvant therapy

Observation

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Brewster et al. 2007	1996-2002	Phase 3 (C)	Retinoic acid & IFN	Seems not superior

No further treatment.

Preceding treatment

• Surgical resection

References

1. Brewster AM, Lee JJ, Clayman GL, Clifford JL, Reyes MJ, Zhou X, Sabichi AL, Strom SS, Collins R, Meyers CA, Lippman SM. Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for patients with aggressive skin squamous cell carcinoma. J Clin Oncol. 2007 May 20;25(15):1974-8. link to original article PubMed

Advanced or metastatic disease, all lines of therapy

Cemiplimab monotherapy

Regimen variant #1, weight-based dose

Study	Years of enrollment	Evidence
Migden et al. 2018 (R2810-ONC-1423)	2016-2017	Phase 1 (RT)
Migden et al. 2018 (R2810-ONC-1540)	2016-2017	Phase 2 (RT)

Note: this is the dose used in Groups 1 & 2.

Immunotherapy

• Cemiplimab (Libtayo) 3 mg/kg IV over 30 minutes once on day 1

14-day cycle for up to 48 cycles (96 weeks)

Regimen variant #2, fixed-dose

FDA-recommended dose

Study	Years of enrollment	Evidence
Migden et al. 2018 (R2810-ONC-1540)	2016-2017	Phase 2 (RT)

Note: this is dose used in Group 3 of the phase II trial.

Immunotherapy

• Cemiplimab (Libtayo) 350 mg IV over 30 minutes once on day 1

21-day cycle for up to 18 cycles (1 year)

References

1. R2810-ONC-1423: Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang ALS, Rabinowits G, Thai AA, Dunn LA, Hughes BGM, Khushalani NI, Modi B, Schadendorf D, Gao B, Seebach F, Li S, Li J, Mathias M, Booth J, Mohan K, Stankevich E, Babiker HM, Brana I, Gil-Martin M, Homsi J, Johnson ML, Moreno V, Niu J, Owonikoko TK, Papadopoulos KP, Yancopoulos GD, Lowy I, Fury MG. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018 Jul 26;379(4):341-351. Epub 2018 Jun 4. link to original article contains verified protocol PubMed NCT02383212
2. R2810-ONC-1540: Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang ALS, Rabinowits G, Thai AA, Dunn LA, Hughes BGM, Khushalani NI, Modi B, Schadendorf D, Gao B, Seebach F, Li S, Li J, Mathias M, Booth J, Mohan K, Stankevich E, Babiker HM, Brana I, Gil-Martin M, Homsi J, Johnson ML, Moreno V, Niu J, Owonikoko TK, Papadopoulos KP, Yancopoulos GD, Lowy I, Fury MG. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018 Jul 26;379(4):341-351. Epub 2018 Jun 4. link to original article contains verified protocol PubMed NCT02760498

Cetuximab monotherapy

Regimen variant #1, weekly, indefinite

Study	Evidence
Maubec et al. 2011 (CTXSCC)	Phase 2

Targeted therapy

• Cetuximab (Erbitux) as follows:
  • Cycle 1: 400 mg/m² IV once on day 1
  • Cycle 2 onwards: 250 mg/m² IV once on day 1

7-day cycle for at least 6 cycles

Regimen variant #2, weekly x 3 mo

Study	Evidence
Kim et al. 2011	Case report

Targeted therapy

• Cetuximab (Erbitux) 400 mg/m² IV once, then 250 mg/m² IV once per week

3-month course

Regimen variant #3, intermittent

Study	Evidence
Miller et al. 2010	Case report

Targeted therapy

• Cetuximab (Erbitux) 400 mg/m² IV once on day 1, then 250 mg/m² IV once per day on days 8, 15, 22

6-month cycles

References

1. Case report: Bauman JE, Eaton KD, Martins RG. Treatment of recurrent squamous cell carcinoma of the skin with cetuximab. Arch Dermatol. 2007 Jul;143(7):889-92. link to original article PubMed
2. Case report: Suen JK, Bressler L, Shord SS, Warso M, Villano JL. Cutaneous squamous cell carcinoma responding serially to single-agent cetuximab. Anticancer Drugs. 2007 Aug;18(7):827-9. link to original article PubMed
3. Case report: Arnold AW, Bruckner-Tuderman L, Zuger C, Itin PH. Cetuximab therapy of metastasizing cutaneous squamous cell carcinoma in a patient with severe recessive dystrophic epidermolysis bullosa. Dermatology. 2009;219(1):80-3. Epub 2009 May 13. link to original article PubMed
4. Case report: Miller K, Sherman W, Ratner D. Complete clinical response to cetuximab in a patient with metastatic cutaneous squamous cell carcinoma. Dermatol Surg. 2010 Dec;36(12):2069-74. Epub 2010 Oct 11. link to original article contains verified protocol PubMed content property of HemOnc.org
5. Case report: Kim S, Eleff M, Nicolaou N. Cetuximab as primary treatment for cutaneous squamous cell carcinoma to the neck. Head Neck. 2011 Feb;33(2):286-8. link to original article contains verified protocol PubMed
6. CTXSCC: Maubec E, Petrow P, Scheer-Senyarich I, Duvillard P, Lacroix L, Gelly J, Certain A, Duval X, Crickx B, Buffard V, Basset-Seguin N, Saez P, Duval-Modeste AB, Adamski H, Mansard S, Grange F, Dompmartin A, Faivre S, Mentré F, Avril MF. 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 Sep 1;29(25):3419-26. Epub 2011 Aug 1. link to original article contains verified protocol PubMed NCT00240682

Cisplatin & Doxorubicin

Regimen

Study	Evidence
Guthrie et al. 1990	Non-randomized

Chemotherapy

• Cisplatin (Platinol) 75 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1

21-day cycles

References

1. Case series: Guthrie TH, Porubsky ES. Successful systemic chemotherapy of advanced squamous and basal cell carcinoma of the skin with cis-diamminedichloroplatinum III and doxorubicin. Laryngoscope. 1982 Nov;92(11):1298-9. link to original article PubMed
2. Case series: Guthrie TH Jr, McElveen LJ, Porubsky ES, Harmon JD. Cisplatin and doxorubicin. An effective chemotherapy combination in the treatment of advanced basal cell and squamous carcinoma of the skin. Cancer. 1985 Apr 15;55(8):1629-32. PubMed
3. Case series: 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 Feb;8(2):342-6. link to original article contains verified protocol PubMed

Cisplatin, Interferon alfa-2a, Isotretinoin

Regimen

Study	Years of enrollment	Evidence
Shin et al. 2002	1993-1999	Phase 2

Note: Shin et al. 2002 did not clearly specify whether the interferon alfa used in the trial was 2a or 2b, but based on the details in the paper and the references cited, it is inferred that interferon alfa-2a was used.

Immunotherapy

• Interferon alfa-2a (Roferon-A) 5,000,000 units/m² SC 3 times per week

Chemotherapy

• Isotretinoin (Accutane) 1 mg/kg PO once per day
• Cisplatin (Platinol) 20 mg/m² IV once per day on days 1, 8, 15, 22

28-day cycles

References

1. Shin DM, Glisson BS, Khuri FR, Clifford JL, Clayman G, Benner SE, Forastiere AA, Ginsberg L, Liu D, Lee JJ, Myers J, Goepfert H, Lotan R, Hong WK, Lippman SM. Phase II and biologic study of interferon alfa, retinoic acid, and cisplatin in advanced squamous skin cancer. J Clin Oncol. 2002 Jan 15;20(2):364-70. link to original article contains verified protocol PubMed

Pembrolizumab monotherapy

Regimen

Study	Years of enrollment	Evidence
Grob et al. 2020 (KEYNOTE-629)	2017-2018	Phase 2 (RT)

Immunotherapy

• Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycle for up to 35 cycles (2 years)

References

1. KEYNOTE-629: Grob JJ, Gonzalez R, Basset-Seguin N, Vornicova O, Schachter J, Joshi A, Meyer N, Grange F, Piulats JM, Bauman JR, Zhang P, Gumuscu B, Swaby RF, Hughes BGM. Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629). J Clin Oncol. 2020 Sep 1;38(25):2916-2925. Epub 2020 Jul 16. link to original article contains verified protocol link to PMC article PubMed NCT03284424

Investigational agents

Drugs with some degree of promising activity in clinical trials.