Treatments Beyond Localized Skin Surgery for BCC, SCC, and Localized Melanoma
Christopher B. Zachary, MBBS, FRCP
Standard treatment for basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and localized melanoma usually includes skin surgery. Several novel treatments that are alternatives to surgery are reviewed briefly here.
Basal Cell Carcinoma
BCC is the most common type of nonmelanoma skin cancer.1 The Hedgehog (Hh) pathway is an essential regulator of growth and development during embryogenesis. This pathway usually is dormant in adulthood and is activated in several cancers, including BCC. Inhibitors of the Hh pathway have proved beneficial for BCC.1,2
Vismodegib
Vismodegib was the first Hh pathway inhibitor approved by the US Food and Drug Administration (FDA) for the treatment of adults with metastatic or locally advanced BCC.3-5 Vismodegib has also demonstrated efficacy in inhibiting the Hh pathway in patients with basal-cell nevus (Gorlin) syndrome.6 Toxicity (most commonly grade 1 and 2 dysgeusia, muscle cramps, hair loss, and weight loss) led roughly half the patients to stop a continuous treatment regimen in the phase 2 trial.6 Two intermittent dosing regimens designed to improve tolerability and safety reduced the number of clinically evident BCC lesions at week 73: 63% fewer BCC lesions with schedule A, 54% fewer BCC lesions with schedule B. Nearly all (95%) patients in the trial developed treatment-related adverse events (AEs), but only 23% discontinued treatment due to AEs.7
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.