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.
ABSTRACT
BACKGROUND: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. OBJECTIVE: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. METHODS: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. RESULTS: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris-like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. CONCLUSIONS: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Drug Eruptions/epidemiology , Neoplasms/drug therapy , Paronychia/epidemiology , Protein Kinase Inhibitors/adverse effects , Adolescent , Canada/epidemiology , Child , Child, Preschool , Drug Eruptions/diagnosis , Drug Eruptions/etiology , Female , Humans , Infant , Male , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Paronychia/chemically induced , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Retrospective Studies , United States/epidemiologyABSTRACT
Allergic contact dermatitis (ACD) is a cutaneous type IV hypersensitivity immune reaction mounted against substances in contact with the skin to which the patient has been sensitized. ACD is common, affecting approximately 72 million Americans per year, and is more common in women. One common contact allergen group is acrylates, which are monomers that are polymerized in the making of glues, adhesives, and plastic materials. It is the monomers that are sensitizing, whereas the final polymers are inert. Acrylates were the 2012 Contact Allergen of the Year with the specific acrylate, isobornyl acrylate, being the 2020 Contact Allergen of the Year. This article reviews the history of acrylate use, epidemiology, and both known and emerging sources of acrylates resulting in ACD.
