Highlights from Saturday, January 25, 2020
Dermatology in Review
Hensin Tsao, MD, PhD, in his inimitable style, discussed the most important findings from the literature that will impact the future of dermatology.
Notable papers discussed in Dr. Tsao’s vast presentation include:
- A randomized clinical trial published in JAMA, in which 24 volunteers were subjected to sunscreen formulations (two spray formulations, one lotion, one cream) containing varying concentrations of avobenzone, oxybenzone, octocylene, and ecamsule; 2mg/cm2 were applied to 75-percent BSA four times per day for four days. Blood samples were collected to determine maximum plasma concentrations and AUC. Oxybenzone exhibited the highest blood concentration and fastest absorption, and all sunscreens exceeded steady state 0.5 ng/ml.
- A randomized trial of four common field-directed treatment approaches for actinic keratosis (AK): 1) 5% fluorouracil cream; 2) 5% imiquimod cream; 3) methyl aminolevulinate photodynamic therapy (MAL-PDT); 4) 0.015% ingenol mebutate gel. The primary outcome of the study was the percent of patients who demonstrated a 75-percent or greater reduction in the number of AKs from baseline to 12 months after the end of treatment. Dr. Taso highlighted that 5%-FU appeared to be the most effective, with a comparatively good tolerability profile, and PDT was the most painful during treatment.
- Five-year follow ups on two major treatment standards for metastatic melanoma: 1) the COMBI trials, which examined 553 patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutation randomized to dabrafenib plus trametinib; and 2) a randomized controlled trial that examined melanoma treatments nivolumab and ipilimumab, alone and in combination with each other.
- A Phase III, double-blind, placebo controlled (N=165) trial that examined the selective kappa opioid receptor agonist difelikefalin, administered intravenously three times per week for 12 weeks, versus placebo for hemodialysis patients with pruritus; the primary outcome was the proportion of patients with an improvement of at least 3 points from baseline at Week 12 on the 24-hour Worst Itching Intensity Numerical Rating Scale (0=none, 10=worse). While Dr. Tsao pointed out the significant placebo effect that appeared to be present in this trial, he doesn’t rule out the importance of this new potential treatment for chronic uremic pruritus, considering there are no drugs currently approved by the US Food and Drug Administration for the condition.
- A multicenter Phase II study evaluating pembrolizumab in relapsed and refractory mycosis fungoides and Sezary Syndrome. Overall response rate in the study was 38 percent, which Dr. Tsao notes is favorable compared to other treatments; he also pointed out that the results were notably durable.
- A whole exome sequencing project to discover variants associated with central centrifugal cicatricial alopecia (CCCS) that found increased frequency of rare peptidyl arginine deiminase 3 (PADI3) variants among patients with CCCA compared to the general population
- A nationwide, population-based Korean cohort study that found a significant cancer-protective effect associated with vitiligo; Dr. Tsao explained that colorectal, lung, and breast cancers were most strongly associated with chemoprotection, while thyroid cancer was most strongly associated with increased risk
In her update of pediatric dermatology, Dr. Friedlander began her presentation with the most recent guidelines of care for infantile hemangiomas (IH) from the American Academy of Pediatrics, including a review of how to choose among the currently available therapies for IH, including propranolol, topical timolol, intralesional triamcinolone, and oral steroids. Dr. Friedlander went on to discuss research on MEK inhibition as a way to improve symptom control in primary NRAS-driven central nervous system melanoma in children, as well as a case report of a giant congenital melanocytic nevus treated with trametinib. Dr. Friedlander moved on to a discussion of topical cannabis for epidermolysis bullosa, then touched on the new joint American Academy of Dermatology-National Psoriasis Foundation guidelines for psoriasis in pediatric patients. An extensive discussion of the latest research on sunscreen absorption rounded out her informative presentation.
New Drugs and Therapies 2020
The “Ted and Neal Show” once again entertained and educated meeting attendees about new drugs and therapies in dermatology and how we will be using them in 2020.
Ted Rosen, MD and Neal Bhatia, MD, discussed a variety of new, emerging, and noteworthy drugs and therapies in their presentation, including topical retinoids for acne, such as trifarotene 0.005% cream, tretinoin 0.05% lotion, and tazarotene 0.045% lotion, the topical antiandrogen clascorterone 1% cream for acne, and minocycline 4.0% foam for acne.
In addition, the presentation covered emerging research on the efficacy of VP-102 0.7% topical cantharidin in a single-use vial for the treatment of molluscum contagiosum, as well as an intravenous formulation of cetirizine for acute urticaria and betamethasone dipropionate 0.064% plus calcipotriene 0.005% for plaque psoriasis.
The first FDA-approved vaccine for the prevention of the Ebola virus disease, a critical milestone in public health preparedness, was discussed, along with microwave therapy for cutaneous human papilloma virus infection.
Following this, the presentation touched on a microencapsulated benzoyl peroxide 5% formulation for inflammatory lesions of rosacea and microencapsulated benzoyl peroxide 3% with tretinoin 0.1% for acne.
After, the pair discussed afamelanotide, an analogue of alpha-melanocyte-stimulating hormone, which produces tanning-like pigmentation and is the first treatment approved to increase pain-free light exposure in patients with erythropoietic protoporphyria.
The presentation wrapped up with a discussion of sofpironium bromide gel for hyperhidrosis and 5-aminolevulinic acid and photodynamic therapy for actinic keratosis on the upper extremities.
Cutaneous Oncology, Part 1
Presentations from George Martin, MD, Ted Rosen, MD, Eggert Stockfleth, MD, and Chrysalyne Schmults, MD, MSCE guided attendees through new therapies in actinic keratosis, ways to optimize the treatment of AKs and non-melanoma skin cancer, including advanced-stage disease.
In his presentation, Dr. Martin explained to attendees the merits of adding calcipotriene 0.05% to 5% fluorouracil (5-FU) in equal parts to improve the efficacy of treating AKs compared to treating with 5% 5-FU alone. Also discussed was tirbanibullin, a new topical field therapy for AKs currently awaiting approval. Tirbanibullin targets tubulin and the Src growth pathways in AKs. Dr. Martin pointed to research in which tirbanibullin was applied twice daily for five days; 50 percent of patients achieved total clearance of their AKs, with remarkably minimal irritation. For long-term chemoprevention in high-risk patients with AK/NMSC, Dr. Martin recommended imiquimod 3.75% or 5% imiquimod for one week, followed by two weeks of rest, then once weekly for maintenance indefinitely. However, Dr. Martin notes that this is not to be used in immunocompromised (SOTR) or autoimmune patients. Dr. Martin also touched upon the withdrawal of ingenol mebutate from the market in the European Union as a result of suspected association of ingenol mebutate with NMSC; however, Dr. Martin notes that causation was not established in patients who have a high risk for NMSC.
In his presentation, titled, “From AK to SCC,” Dr. Stockfleth reviewed the interaction between human papillomavirus (HPV)23 E6 and homeodomain-interacting protein kinase 2 (HIPK2) and the role this interaction plays in the development of skin cancer. Research on histological intralesional heterogeneity of actinic keratosis and how this relates to field cancerization was also discussed. Dr. Stockfleth closed his presentation with a review of research evaluating two histological classifications for actinic keratoses.
In Dr. Schmults’ presentation, she discussed tumor staging systems, including a comparison of the 7thand 8theditions of the American Joint Committee on Cancer (AJCC) staging system, and how both compare to Brigham and Women’s Hospital Staging System, which appeared to outperform both AJCC7 and AJCC8 in a Norwegian validation study. Dr. Schmults moved on to therapies for advanced unresectable cutaneous squamous cell carcinoma, including anti-PD-1 therapy after surgery and radiation fail and cemiplimab.