Which systemic chemotherapy agents are used to treat of cutaneous squamous cell carcinoma (cSCC), and what immunotherapies can be used in cSCC?

Updated: Jul 08, 2020
  • Author: Talib Najjar, DMD, MDS, PhD; Chief Editor: Arlen D Meyers, MD, MBA  more...
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A variety of different chemotherapeutic agents have been used to treat metastatic cSCC. Although many of these agents have an established role in chemotherapy for mucosal head and neck squamous cell carcinoma, high-quality data is frequently lacking for their use in cSCC. Among the most common nontargeted agents used in cSCC are cisplatin and carboplatin, 5-FU, and taxanes.

Cetuximab, a chimeric immunoglobulin G1 monoclonal antibody that inhibits EGFR, has been reported as successful in multiple case reports [49, 50, 51, 52] High-quality studies examining these agents in high-risk cSCC are needed.


Immunotherapy, especially with programmed death ligand 1 (PD-L1) inhibitors, may be considered in advanced cSCC. The programmed death 1 (PD-1) receptor is expressed on T cells, binding to its ligand (PD-L1) and inhibiting T-lymphocyte functions. PD-L1 is expressed in cSCC tumors, and its expression correlates with risk of metastasis. [4]

Approved by the US Food and Drug Administration (FDA) in October 2018, the PD-L1 inhibitor cemiplimab (Libtayo) became the first treatment specifically approved for patients with metastatic or locally advanced cSCC who are not candidates for curative surgery or curative radiation.

Approval followed results from EMPOWER-CSCC-1, a multicenter, open-label, nonrandomized phase 2 trial, and two advanced expansion cohorts. The investigators found an objective response rate of 47% among patients with metastatic disease, and 49% in those with locally advanced cSCC. [53]

In June 2020, the FDA approved pembrolizumab (Keytruda) for the treatment of patients with recurrent or metastatic cSCC that is incurable via surgery or radiation.

Approval was based on efficacy data from the multicenter, nonrandomized, open-label KEYNOTE-629 clinical trial. Patients (n=105) received pembrolizumab 200 mg IV every 3 weeks until the disease progressed, toxicity became unacceptable, or a maximum of 24 months had passed, with the cohort demonstrating an objective response rate of 34%. [54]

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