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Treatment & Management

Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that is becoming more frequent worldwide.1

Early-Stage and Low-Risk cSCC1

  • Treatment: Usually managed with surgery and sometimes other localized treatments
  • Outlook: These cases are often easier to treat and manage

Advanced cSCC:

  • Locally Advanced or Metastatic cSCC1: These forms can be more serious and harder to treat, leading to higher risks of complications and death
  • Treatment2: Requires a different approach, which may include:

Surgical Resection

Removing the cancer through surgery

Lymph Node Dissection

Removing nearby lymph nodes if the cancer has spread

Adjuvant Radiation Therapy

Additional radiation treatment, sometimes combined with other medications that travel through the bloodstream to reach cancer cells throughout the body

Managing advanced cSCC involves a team of specialists working together to create the best treatment plan. Here’s a breakdown of the main treatment options:

Targeted Therapy

Epidermal growth factor receptor (EGFR) Inhibitors are drugs that target specific proteins on cancer cells to stop their growth. Examples include:

  • Cetuximab: Shows a 28% response rate, with an average survival of 8.1 months3
  • Panitumumab: Shows a 31% response rate4
  • Gefitinib and Erlotinib: Used often with surgery or radiation, with varied effectiveness1
  • Lapatinib: Targets HER2 protein, showing promising results in early trials5

Side effects can include skin problems and diarrhea. Resistance to these drugs can occur, so combinations with other treatments are often explored.1

Systemic Immunotherapy

The immune system is designed to protect your body from harmful invaders while avoiding attacks on healthy cells. It does this using “checkpoint” proteins on immune cells, which act like switches that turn the immune response on or off.6

Cancer cells can sometimes manipulate these checkpoints to avoid being attacked by the immune system. However, certain drugs called checkpoint inhibitors can block these proteins, helping the immune system to find and destroy cancer cells.6

Two important drugs that target a checkpoint protein called PD-1 are cemiplimab and pembrolizumab. PD-1 is a protein on immune cells known as T cells, which usually helps prevent these cells from attacking other cells in the body. By blocking PD-1, these drugs can enhance the immune system’s ability to attack cancer cells.6

Figure. PD-L1 is found on tumor cells, while PD-1 is found on immune cells called T cells. When PD-L1 on the tumor cell binds to PD-1 on the T cell, it blocks essential cell survival signaling pathways, effectively inhibiting the cytotoxic T cell. This inhibition deactivates the protective function of the T cell, enabling the tumor cell to grow. Cemiplimab and pembrolizumab prevent this process by blocking PD-1 or PD-L1, allowing the immune cells to eliminate the tumor cells.7

Cemiplimab

  • Approved for advanced cSCC when surgery isn’t an option
  • In clinical trials, it shows a 50% response rate, with 65% of patients seeing lasting control of their disease8
  • Ongoing long-term studies show an observed objective response rate in 62%, with 22% of patients achieving complete response and 40% achieving partial response at a median follow-up of 22.4 months9
  • Side effects can include fatigue, diarrhea, and nausea9

Pembrolizumab

  • Approved for recurrent or advanced cSCC when surgery isn’t possible
  • In clinical trials, it shows a response rate of 25%, and partial response of 40% at a follow-up of more than 5 years months and manageable side effects3,10
  • Side effects can include fatigue, itching, and weakness10

These therapies have shown promise in improving outcomes and quality of life for patients with advanced cSCC. Ongoing research continues to enhance these treatment strategies, offering hope for better management of this challenging condition.

References

  1. Aboul-Fettouh N, Morse D, Patel J, Migden MR. Immunotherapy and systemic treatment of cutaneous squamous cell carcinoma. Dermatol Pract Concept. 2021;11(suppl 2):e2021169S. doi:10.5826/dpc.11S2a169S
  2. National Comprehensive Cancer Network®. NCCN Clinical Practice Guidelines in Oncology. Squamous Cell Skin Cancer. Version 2.2025. (https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf).
  3. Maubec E, Boubaya M, Petrow P, et al. Phase II study of pembrolizumab as first-line, single-drug therapy for patients with unresectable cutaneous squamous cell carcinomas. J Clin Oncol. 2020;38:3051-3061. doi:10.1200/JCO.19.03357
  4. Foote MC, McGrath M, Guminski A, et al. Phase II study of single-agent panitumumab in patients with incurable cutaneous squamous cell carcinoma. Ann Oncol. 2014;25:2047-2052. doi:10.1093/annonc/mdu368
  5. Strickley JD, Spalding AC, Haeberle MT, Brown T, Stevens DA, Jung J. Metastatic squamous cell carcinoma of the skin with clinical response to lapatinib. Exp Hematol Oncol. 2018;7:20. doi:10.1186/s40164-018-0111-z
  6. American Cancer Society. Immunotherapy for Advanced Basal or Squamous Cell Skin Cancers. Last revised December 16, 2024 (https://www.cancer.org/cancer/types/basal-and-squamous-cell-skin-cancer/treating/immunotherapy.html).
  7. Angelousi A, Chatzellis E, Kaltsas G. New molecular, biological, and immunological agents inducing hypophysitis. Neuroendocrinology. 2018;106:89-100. doi:10.1159/000480086
  8. Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379:341-351. doi:10.1056/NEJMoa1805131

  9. Rischin D, Hughes BGM, Basset-Séguin N, et al. High response rate with extended dosing of cemiplimab in advanced cutaneous squamous cell carcinoma. J Immunother Cancer. 2024;12(3):e008325. doi:10.1136/jitc-2023-008325

  10. Muñoz Couselo E, Hughes BGM, Mortier L, et al. Pembrolizumab (pembro) for locally advanced (LA) or recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC): Long-term results of the phase 2 KEYNOTE-629 study. J Clin Oncol. 2024;42(16_suppl):9554. doi:10.1200/JCO.2024.42.16_suppl.9554

All URLs accessed April 24, 2025

What is cSCC?

Advanced cSCC

Living with cSCC

Treatment & Management

The cSCC Team

FAQs

Reading and Resources

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