Journal of Clinical and Aesthetic Dermatology

APR 2017

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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16 radiotherapy was successfully treated with the oral Hedgehog signalling pathway inhibitor vismodegib. PMID: 27905158 Targeting the Hedgehog pathway for locally advanced and metastatic basal cell carcinoma. Yin VT, Esmaeli B. Curr Pharm Des. 2016 Dec 7. [Epub ahead of print] Synopsis: Authors review the practice of targeting the Hedgehog pathway in basal cell carcinoma patients for whom surgery is not an option. They also discuss response rates and side effects of vismodegib and sonidegib, the two FDA- approved sonic Hedgehog inhibitor drugs. PMID: 27928965 Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade. Lipson EJ, Lilo MT, Ogurtsova A, et al. J Immunother Cancer. 2017;5:23. eCollection 2017 Mar 21. Synopsis: To explore the use of pembrolizumab to provoke an anti-tumor response in basal cell carcinoma via expression of programmed death-ligand 1 (PD-L1), a transmembrane protein that may help suppress the immune system, authors report on treatment response in a patient with advanced basal cell carcinoma. They also examined 40 basal cell carcinoma specimens. They found that specimens demonstrated PD-L1 expression on tumor cells (n=9, 22%) and on tumor-infiltrating lymphocytes and associated macrophages (n=33, 82%). Authors conclude that anti-PD-1 therapy should be tested in patients with advanced basal cell carcinoma as initial treatment or after acquired resistance to hedgehog pathway inhibition PMID: 28344809; PMCID: PMC5360064 Two intermittent vismodegib dosing regimens in patients with multiple basal cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial. Dréno B, Kunstfeld R, Hauschild A, et al. Lancet Oncol. 2017;18(3):404–412. Epub 2017 Feb 8. Synopsis: Investigators report results to- date of an ongoing randomized, regimen- controlled, double-blind, phase 2 trial exploring two long-term intermittent vismodegib dosing regimens in patients with multiple basal cell carcinomas: 12/8/12 weeks (n=116) versus 24/8/8 (n=113) weeks of treatment/placebo/treatment. They found that both regimens showed good activity (reduction in mean lesions of 54–63%) and recommend further study. PMID: 28188086 Inhibition of the hedgehog pathway in patients with basal-cell nevus syndrome: final results from the multicentre, randomised, double- blind, placebo-controlled, phase 2 trial. Tang JY, Ally MS, Chanana AM, et al. Lancet Oncol. 2016;17(12):1720–1731. Epub 2016 Nov 10. Synopsis: Here, researchers report the final results of a multicenter, randomized, double-blind, placebo- controlled, phase 2 trial comparing the effect of oral vismodegib (n=26) to placebo (n=15) on the incidence of new surgically eligible basal cell carcinomas after three months of treatment. They found that the vismodegib group presented significantly fewer surgically eligible basal cell carcinomas per patient per year, and crossover of the patients originally assigned to placebo also showed reduced development of new lesions. Authors conclude that vismodegib reduced basal cell carcinoma tumor burden in patients with basal cell nevus syndrome, although vismodegib- associated adverse events frequently led to interruption of treatment, in turn followed by basal cell carcinoma recurrence. PMID: 27838224 Characterization and management of Hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma. Lacouture ME, et al. Oncologist. 2016;21(10):1218–1229. Review. Synopsis: To help clinicians counsel and care for patients with advanced basal cell carcinoma, authors discuss the incidence, clinical presentation, putative mechanisms, and management strategies for adverse events related to administration of Hedgehog pathway inhibitors. PMID: 27511905; PMCID: PMC5061532 Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness. Silapunt S, et al. Ther Adv Med Oncol. 2016;8(5):375–382. Synopsis: Here, authors discuss the use of two FDA-approved Hedgehog pathway inhibitors with anti-tumor activity in advanced basal cell carcinoma, including safety profiles and common adverse effects. PMID: 27583029; PMCID: PMC4981290 JCAD journal of clinical and aesthetic dermatology April 2017 • Volume 10 • Number 4 JOURNAL WATCH (continued)

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