Cemiplimab for the Treatment of Advanced Cutaneous Squamous Cell Carcinoma: Appropriate Patient Selection and Perspectives

Abstract

Five percent of patients with cutaneous squamous cell carcinoma develop locally advanced or metastatic disease that is not amenable to definitive surgical or radiation therapy. Cemiplimab, an antibody against programmed death receptor-1, was approved in the United States for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma in 2018. We performed a literature review on the use of cemiplimab in cutaneous squamous cell carcinoma, with an emphasis on efficacy, safety and tolerability, patient selection, and future directions. Embase and PubMed were searched for relevant terms, and 23 peer-reviewed journal articles presenting primary data on cemiplimab treatment in 5 or more subjects with cutaneous squamous cell carcinoma were included and summarized. Objective response rates in locally advanced and metastatic disease ranged from 42.9% to 50.8% in Phase I/ II clinical trials and 32-77% (median 58%) in post-approval observational studies. Phase II trials looking at neoadjuvant use also had favorable response rates. Real-world studies demonstrated cemiplimab efficacy in periorbital tumors, tumors with large caliber perineural invasion, and tumors in solid organ transplant recipients. Cemiplimab was safe and well-tolerated in most patients. While side effects such as fatigue, diarrhea, pruritus, and rash were fairly common, only 9.8% of adverse events required cessation of therapy in phase II trials. Severe adverse events were primarily immune-mediated, including pneumonitis, myocarditis, myositis, and autoimmune hepatitis; the risk of treatment-related death was 3% in clinical trials. Further research on cemiplimab therapy in cutaneous squamous cell carcinoma is needed, and trials are now underway to obtain Phase IV long-term real-world data, further data on adjuvant and neoadjuvant use, and additional data in special populations such as stem cell and solid organ transplant recipients.

Exploring Costimulatory Blockade-Based Immunologic Strategies in Transplantation: Are They a Promising Immunomodulatory Approach for Organ and Vascularized Composite Allotransplantation?

“…Immunotherapy has transformed the management of severe cancers, including cutaneous squamous cell carcinoma (CSCC). Cemiplimab, which acts as a PD-1 immune checkpoint inhibitor, has been approved by the FDA for treating locally advanced and metastatic cutaneous squamous cell carcinoma (CSCC) [ 157 ]. This type of tumor frequently arises as a complication in patients who are chronically immunosuppressed following a transplant.…”

A Novel Intersection - Cytomegalovirus Gastritis Following Cemiplimab and Talimogene Laherparepvec in a Patient with Advanced Cutaneous Squamous Cell Carcinoma: a Case Report

“…In 2018, the Food and Drug Administration (FDA) approved cemiplimab (LIBTAYO, Regeneron Pharmaceuticals Inc.), an antibody against programmed cell death receptor-1 (anti-PD-1), for such advanced skin SCC cases. Phase I/II clinical trials showed response rates between 42.9% and 50.8% for locally advanced and metastatic disease, and observational studies post-approval documented rates of 32-77% (median 58%) [5].…”

Cemiplimab-Induced Hyperosmolar Hyperglycemic State With Concurrent Diabetic Ketoacidosis in a Patient Receiving Treatment for Cutaneous Squamous Cell Carcinoma

“…Cutaneous squamous cell carcinoma (CSCC) is the second most common nonmelanoma skin cancer, which accounts for 20% of all skin cancers [1]. While most CSCCs are treated with surgical intervention, approximately 5% display an aggressive phenotype that is not amenable to surgery or radiation therapy [2]. This paved the way for exploring immunotherapy options to treat advanced cases of CSCC.…”

“…The use of cemiplimab in laCSCC and mCSCC has shown excellent objective response rates with good tolerability [4][5][6]. Although cemiplimab shows good efficacy in patients with CSCC, it has been associated with side effects such as fatigue, diarrhea, anemia, rash, pruritus, musculoskeletal pain, pneumonia, and pancreatitis [2]. On rare occasions, cemiplimab can give rise to potentially life-threatening endocrinopathies such as diabetic ketoacidosis (DKA) [2].…”