Non-Melanoma Skin Cancer
Pat Price, Karol Sikora in Treatment of Cancer, 2020
For patients with extensive SCC that has relapsed after conventional surgery or RT or for metastatic disease, a variety of drugs, including bleomycin, methotrexate, actinomycin, vincristine, vinblastine, fluorouracil (5-FU), and hydroxyurea, have been used with varying degrees of success.166 The most commonly used are cisplatin, carboplatin, and 5-FU, either as monotherapy or in combination regimens.167–169 Cisplatin has been used as monotherapy and in combination with other cytotoxic drugs in advanced lesions and metastatic cutaneous SCC. Eleven patients with advanced BCC or SCC of the skin were treated with cisplatin (75 mg/m2, intravenous [IV]) plus doxyrubicin (50 mg/m2, IV) at 3-week intervals. Responses were seen after 10–12 courses, and five of the 11 patients were in remission at the time of report.165 A combination of cisplatin, 5-FU, and bleomycin produced partial or complete remission (CR) in 11/14 patients with advanced cutaneous SCC.170 The search for more active combinations continues. A Phase II study of interferon-α (IFN-α), retinoic acid, and cisplatin in 39 patients with advanced SCC of the skin showed an overall response rate (ORR) of 34% with a median duration of response of 9 months.171 In August 2019, Cemiplimab, a monoclonal antibody that binds the programmed death receptor-1 (PD-1), has become available in the UK under Cancer Drug Fund for the treatment of locally advanced or metastatic cutaneous SCC.
Squamous Cell Carcinoma
Debjani Sahni, Adam Lerner, Bilal Fawaz in Advanced Skin Cancer, 2022
Systemic therapies are used mostly for metastatic cSCCs but are also considered for unresectable disease or when RT is not possible. In recent years, two classes of therapies have emerged for cSCC treatment: Targeted and immunologic therapies. The main targeted therapy is in the form of EGFR inhibitors (e.g., cetuximab). EGFR is expressed in more than 90% of cSCC and is responsible for cellular proliferation, survival, angiogenesis, and metastasis. In 2006, the FDA approved cetuximab for the treatment of locally advanced or metastatic mucosal SCC. Its use in cSCC is still off-label. The other form of systemic treatment currently approved for use in cSCC is checkpoint inhibitor immunotherapy, specifically the PD-1 inhibitor cemiplimab.12
Antibody-Based Therapies
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Developed jointly by Regeneron and Sanofi, cemiplimab (LibtayoTM) was approved by the FDA in 2018 for the treatment of metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC in patients who are not candidates for curative surgery or radiotherapy. It is currently being studied in multiple clinical trials, including Phase III clinical trials in patients with cervical and non-small-cell lung cancer. At the time of writing, Phase II studies are also underway in patients with basal cell, head and neck, liver, oropharyngeal, and prostate cancer, and glioblastoma. Phase I studies are also underway in ovarian, fallopian tube and peritoneal cancers, and multiple myeloma.
Management of periocular cutaneous squamous cell carcinoma with perineural invasion: a case series and literature review
Published in Orbit, 2022
Thomas J. E. Clark, Gerald J. Harris
The use of systemic chemotherapy in the treatment of high-risk cutaneous SCC is increasing as new agents emerge. Platinum-based drugs (e.g., cisplatin and carboplatin) continue to be first-line agents for SCCHN.24 Cetuximab, a chimeric monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has gained more widespread use following a landmark study by Bonner et al.32 The authors reported significantly improved locoregional control, overall survival, and progression-free survival with definitive RT + cetuximab compared to RT alone in stage III–IV nonmetastatic SCC of the oropharynx, hypopharynx, or larynx. Cemiplimab, a human monoclonal antibody directed against the programmed death 1 (PD-1) ligand, recently gained approval by the FDA and the European Medicines Agency.33 In Phase 1 and 2 studies, respectively, the agent induced positive responses in 13 of 26 patients with locally advanced or metastatic cutaneous SCC, and in 28 of 59 patients with metastatic cutaneous SCC.34
Combination regimens and immunologic mechanisms to enhance the efficacy of cemiplimab for cutaneous squamous cell carcinoma
Published in Expert Review of Anticancer Therapy, 2022
Hannah L. Hanania, Daniel J. Lewis
We read with interest the review article, ‘Cemiplimab for locally advanced cutaneous squamous cell carcinoma: safety, efficacy, and position in therapy’ by Lebas et al. The authors discuss the role of cemiplimab as a first-line systemic therapy for locally advanced cutaneous squamous cell carcinoma (cSCC) when surgery and/or radiotherapy are insufficient. Cemiplimab is a recombinant IgG4 human monoclonal antibody against PD-1 and one of the two FDA-approved treatments for locally advanced and metastatic cSCC in addition to pembrolizumab. These monoclonal antibodies block PD-1, thereby producing a heightened CD8+ cell-mediated response. Cemiplimab was found to have an objective response rate of 47% [1]. This response rate may be increased with the addition of immunologic therapies such as Toll-like receptor (TLR) agonists including imiquimod or intralesional TLR agonists, interleukin (IL)-2, IL-12, and interferon (IFN) to augment the anti-tumor response [2,3]. We believe further study and consideration of cemiplimab in combination with these immunologic therapies are warranted for locally advanced and metastatic cSCC.
Cemiplimab for the treatment of advanced cutaneous squamous cell carcinoma
Published in Expert Opinion on Drug Safety, 2022
Alessia Villani, Sonia Sofia Ocampo-Garza, Luca Potestio, Gabriella Fabbrocini, Jorge Ocampo-Candiani, Jorge Ocampo-Garza, Massimiliano Scalvenzi
PD-1 is an inhibitory receptor expressed on activated B and T lymphocytes and myeloid cells[21]. Its engagement with the ligands PD-L1 and PD-L2 leads to an inhibitory signal, causing immune tolerance[22]. The upregulation of PD-1 in CSCC contributes to the inhibition of active T-cell immune surveillance of tumors[8]. Cemiplimab is a recombinant human immunoglobulin G4 (IgG4) monoclonal antibody targeting PD-1[20], it acts by binding and blocking PD-1´s interaction with PD-L1 and PD-L2 in order to increase the anti-tumor immune response[20]. It has high affinity for human PD-1. Indeed, equilibrium dissociation constants (KD) of cemiplimab, assessed through surface plasmon resonance in in vitro experiments is 6.11 nmol/L for monomeric human PD-1-mmH and 628 pmol/L for dimeric human PD-1-mFc proteins, respectively[23]. The binding of cemiplimab to PD-1 on activated primary human CD3þ T cells has been confirmed through flow cytometric analysis[23]. Competition sandwich ELISA exhibited that cemiplimab inhibits the binding of both human PD-1-mFc and cynomolgus monkey PD-1-mFc to plate-bound human PD- L1-hFc (IC50 values of 0.60 and 0.97 nmol/L) and human PD-L2-hFc (IC50 0.13 and 0.22 nmol/L)[23]. Moreover, it does not intervenes neither in antibody-dependent cell-mediated cytotoxicity activity nor in complement-dependent cytotoxicity. [23] Additionally, in vitro studies demonstrated that cemiplimab induces a dose-dependent increase in T-cell proliferation[23].
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