Treatments Beyond Localized Skin Surgery for BCC, SCC, and Localized Melanoma
Sonidegib
Another Hh pathway inhibitor, sonidegib, is FDA-approved for the treatment of adult patients with locally advanced BCC that has recurred after surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.8,9 In a phase 2 trial, 36% of patients receiving a lower dose and 34% of patients receiving a higher dose had an objective response.8
Curettage Without Electrodesiccation
Curettage offers an option to treat small BCC tumors. Nearly all (96% of 302) BCC tumors treated with curettage by one physician showed no recurrence at 5 years. Compared with electrodesiccation, curettage alone was associated with minimal scarring and less hypopigmentation.10 These findings are of particular interest given the recent JAMA Dermatology publication questioning the appropriate-use criteria for superficial BCCs.11
Squamous Cell Carcinoma
Approximately 1.5% of patients with cutaneous SCC (cSCC) will die, for an estimated total of between 4000 and 8800 US deaths in 2012.12 An alternative staging system proposed for cSCC can improve identification of the subset of tumors with a high risk for metastasis and death.13 Three alternative treatment options for SCC exist: topical fluorouracil (5-FU) and calcitriol,14 intralesional methotrexate (MTX),15 and cemiplimab.16
Topical 5-FU and Calcitriol
In a randomized trial involving 131 patients, applying topical 5% 5-FU cream plus 0.005% calcipotriol ointment twice daily for 4 days significantly reduced the number of actinic keratoses (mean reduction, 88% vs 26% for Vaseline®; P<0.0001). Participants applied the treatment to the face, scalp, and upper extremities.14 The treatment induced thymic stromal lymphopoietin (TSLP), human leukocyte antigen (HLA) class II, and natural killer cell group 2D (NKG2D) ligand expression in the lesional keratinocytes. These changes were associated with marked CD4+ T-cell infiltration that peaked on days 10 to 11 after treatment, without pain, crusting, or ulceration. The investigators concluded that the synergistic effects of calcipotriol and 5-FU treatment activated CD4+ T-cell–mediated immunity against actinic keratoses.14
Highlights of the 43rd Annual Hawaii Dermatology Seminar
This journal supplement is intended for dermatologists, nurse practitioners, registered nurses, physician assistants, and other clinicians who practice medical dermatology and aesthetic medicine.
Supported by educational grants from:
Ortho Dermatologics, LEO Pharma Inc., and Galderma Laboratories, L.P.
Activity Information
Expired
Original Release Date: August 2019
Expiration Date: August 31, 2021
Estimated Time to Complete Activity: 2.0 hours
Expired
Participants should read the activity information, review the activity in its entirety, and complete the online post-test and evaluation. Upon completing this activity as designed and achieving a passing score on the post-test, you will be directed to a Web page that will allow you to receive your certificate of credit via e-mail or you may print it out at that time.
The online post-test and evaluation can be accessed at https://tinyurl.com/HDS19Supp.
Inquiries about continuing medical education (CME) accreditation may be directed to the University of Louisville Office of Continuing Medical Education & Professional Development (CME & PD) at [email protected] louisville.edu or 502-852-5329.
CME/CE Accreditation Statements
Physicians: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the University of Louisville School of Medicine and Global Academy for Medical Education, LLC. The University of Louisville School of Medicine is accredited by the ACCME to provide continuing education for physicians.
The University of Louisville School of Medicine designates this enduring activity for a maximum of 2.0 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Nurses
Joint Provider Accreditation Statement
In support of improving patient care, this activity has been planned and implemented by Postgraduate Institute for Medicine and Global Academy for Medical Education, LLC. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the health care team.
Continuing Nursing Education
The maximum number of hours awarded for this Continuing Nursing Education activity is 2.5 contact hours. Designated for 2.4 hours of pharmacotherapy credit for advanced practice nurses.
Educational Needs
Dermatologists can benefit from education on recent developments in many areas of clinical practice. In psoriasis treatment, nearly all patients are prescribed topical therapies. New medications using improved vehicles and fixed-dose combinations have become available, and more are in development. New research linking psoriasis and risk of cardiovascular disease has provided a better understanding of the underlying pathological mechanism and the potential benefit of anti-inflammatory treatment. Recent epidemiologic data on atopic dermatitis in adults have important implications for diagnosis and treatment. In acne treatment, several efficacious systemic treatments are underutilized, and education on their risks and benefits may improve clinical practice. In the treatment of skin cancer, dermatologists should consider several systemic treatments in addition to surgery. Finally, a new botulinum toxin became available recently, and others are in development.
Learning Objectives
At the conclusion of this activity, participants should be better able to:
- Describe recent data on psoriasis treatment, including new vehicles for topical treatments, fixed-dose combination therapies, and investigational topical medications
- Review the relationship between psoriasis and cardiovascular disease (CVD) and the potential effects of psoriasis treatment on CVD risk
- Describe current research on the temporal patterns of atopic dermatitis onset and resolution and the differences in diagnosis and treatment approach for adult and pediatric patients
- Analyze the efficacy and safety of systemic therapies for acne
- Assess the current nonsurgical treatments for basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and localized melanoma
- Review the options for confirming the diagnosis and data on the use of topical and systemic treatments in the management of onychomycosis
- Assess the advantages and disadvantages of available botulinum toxins used to address patient concerns about facial aging
Disclosure Declarations
Individuals in a position to control the content of this educational activity are required to disclose: (1) the existence of any relevant financial relationship with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients with the exemption of nonprofit or government organizations and non–health-carerelated companies, within the past 12 months; and (2) the identification of a commercial product/device that is unlabeled for use or an investigational use of a product/device not yet approved.
Nathaniel J. Jellinek, MD, has indicated he has nothing to disclose.
Michael S. Kaminer, MD, has indicated he is a Consultant for Artic Fox, Cutera, Cytrellis, Endo, L’Oréal, Soliton, and Zeltiq.
Alan Menter, MD, has indicated he is on the Speakers Bureau for AbbVie, Celgene, Eli Lilly, Janssen, Novartis, and OrthoDoc.
Jonathan I. Silverberg, MD, PhD, MPH, has indicated he is on the Speakers Bureau for Regeneron/Sanofi; is a Consultant, and/or Advisory Board member for AbbVie, AnaptysBio, Asana, Dermavant, Eli Lilly, Galderma, GlaxoSmithKline, Glenmark, Kiniksa, LEO, Menlo, Pfizer, Realm, and Regeneron Sanofi; and has received Grant/Contracted Research Support from GlaxoSmithKline.
Linda F. Stein Gold, MD, has indicated she is on the Speakers Bureau for Galderma, LEO, Mayne, Pfizer, Sanofi/Regeneron, Taro, and Valeant; is a Consultant for Foamix, Galderma, LEO, Mayne, Menlo, Pfizer, Sanofi/ Regeneron, Sol-Gel, Taro, and Valeant; and has received Grant/Contracted Research Support from Foamix, Janssen, LEO, Menlo, Pfizer, and Valeant.
Christopher B. Zachary, MBBS, FRCP, has indicated he is a Consultant for Allergan, Candela, Sciton, and Solta.
University of Louisville CME & PD Advisory Board and Staff Disclosures: The University of Louisville CME & PD Advisory Board and office staff have nothing to disclose, with the following Board Member exceptions: Sathya Krishnasamy, MD – Novo Nordisk (Grant Funding); Ashlee Bergin, MD – Merck Pharmaceuticals (Speaking); Michael Sowell, MD – Amgen (Speaking) and Impax Pharmaceuticals (Grant Funding); Rainer Lenhardt, MD – CSL Behring, Mallinckrodt, and Merck (Speaking).
CME/CE Reviewers: Courtney R. Schadt, MD, Assistant Professor of Medicine, Chief of Dermatology, University of Louisville School of Medicine, Louisville, Kentucky, has nothing to disclose.
Postgraduate Institute of Medicine planners and managers have nothing to disclose.
Global Academy for Medical Education Staff: Shirley V. Jones, MBA; Eileen A. McCaffrey, MA; and Margaret McLaughlin, PhD, have nothing to disclose.
Off-Label/Investigational Use Disclosure
This CME/CE activity discusses the off-label use of certain approved medications as well as data from clinical trials on investigational agents. Such material is identified within the text of the articles.
References
- Cirrone F, Harris CS. Vismodegib and the hedgehog pathway: a new treatment for basal cell carcinoma. Clin Ther. 2012;34(10):2039-2050.
- Gould SE, Low JA, Marsters JC Jr, et al. Discovery and preclinical development of vismodegib. Expert Opin Drug Discov. 2014;9(8):969-984.
- Erivedge [package insert]. South San Francisco, CA: Genentech, Inc; January 2012.
- Fosko SW, Chu MB, Mattox AR, Richart JM, Burkemper NM, Slutsky JB. Lichenoid reaction as a potential immune response marker of intratreatment histological response during successful vismodegib treatment for a giant basal cell carcinoma. Dermatol Ther. 2015;28(6):359-362.
- Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171-2179.
- Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012;366(23):2180-2188.
- Dréno B, Kunstfeld R, Hauschild A, et al. Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial. Lancet Oncol. 2017;18(3):404-412.
- Migden MR, Guminski A, Gutzmer R, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol. 2015;16(6):716-728.
- Odomzo [package insert]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc; May 2019.
- Barlow JO, Zalla MJ, Kyle A, DiCaudo DJ, Lim KK, Yiannias JA. Treatment of basal cell carcinoma with curettage alone. J Am Acad Dermatol. 2006;54(6):1039-1045.
- Steinman HK, Dixon A, Zachary CB. Reevaluating Mohs surgery appropriate use criteria for primary superficial basal cell carcinoma. JAMA Dermatol. 2018;154(7):755-756.
- Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 2013;68(6):957-966.
- Jambusaria-Pahlajani A, Kanetsky PA, Karia PS, et al. Evaluation of AJCC tumor staging for cutaneous squamous cell carcinoma and a proposed alternative tumor staging system. JAMA Dermatol. 2013;149(4):402-410.
- Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127(1):106-116.
- Annest NM, VanBeek MJ, Arpey CJ, Whitaker DC. Intralesional methotrexate treatment for keratoacanthoma tumors: a retrospective study and review of the literature. J Am Acad Dermatol. 2007;56(6):989-993.
- Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379(4):341-351.
- Libtayo [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc; September 2018.
- Fosko SW, Navarrete-Dechent CP, Nehal KS. Lentigo maligna—challenges, observations, imiquimod, confocal microscopy, and personalized treatment. JAMA Dermatol. 2018;154(8):879-881.
- Donigan JM, Hyde MA, Goldgar DE, Hadley ML, Bowling M, Bowen GM. Rate of recurrence of lentigo maligna treated with off-label neoadjuvant topical imiquimod, 5%, cream prior to conservatively staged excision. JAMA Dermatol. 2018;154(8):885-889.
Disclosures
Christopher B. Zachary, MBBS, FRCP, has indicated he is a Consultant for Allergan, Candela, Sciton, and Solta.