Hedgehog inhibitors in the treatment of advanced basal cell carcinoma: risks and benefits

References

• Mohan SV, Chang ALS. Advanced basal cell carcinoma: epidemiology and therapeutic innovations. Curr Dermatol Rep. 2014;3(1):40–45.
   PubMedGoogle Scholar
• Rogers HW, Weinstock MA, Harris AR, et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol. 2010;146:283–287.
   PubMed Web of Science ®Google Scholar
• Youssef KK, Van Keymeulen A, Lapouge G, et al. Identification of the cell lineage at the origin of basal cell carcinoma. Nat Cell Biol. 2010;12(3):299–305.
   PubMed Web of Science ®Google Scholar
• Armstrong BK, Kricker A. The epidemiology of UV induced skin cancer. J Photochem Photobiol B. 2001;63(1–3):8–18.
   PubMed Web of Science ®Google Scholar
• Niebel D, Sirokay J, Hoffmann F, et al. Clinical management of locally advanced basal-cell carcinomas and future therapeutic directions. Dermatol Ther (Heidelb). 2020;10(4):835–846.
   PubMed Web of Science ®Google Scholar
• Gorlin RJ, Goltz RW. Multiple nevoid Basal-cell epithelioma, jaw cysts and bifid rib. N Engl J Med. 1960 May;5:908–912.
   Google Scholar
• Migden MR, Chang AL, Dorox L, et al. Emerging trends in the treatment of advanced basal cell carcinoma. Cancer Treat Rev. 2018;64:1–10.
   PubMed Web of Science ®Google Scholar
• Villani A, Fabbrocini G, Cappello M, et al. Real-Life effectiveness of vismodegib in patients with metastatic and advanced basal cell carcinoma: characterization of adverse events and assessment of health-related quality of life using the Dermatology Life Quality Index (DLQI) test. Dermatol Ther (Heidelb). 2019;9(3):505–510.
   PubMed Web of Science ®Google Scholar
• Trakatelli M, Morton C, Nagore E, et al. Update of the European guidelines for basal cell carcinoma management. Eur J Dermatol. 2014;24(3):312–329.
   PubMed Web of Science ®Google Scholar
• Lear JT, Corner C, Dziewulski P, et al. Challenges and new horizons in the management of advanced basal cell carcinoma: a UK perspective. Br J Cancer. 2014;111:1476–1481.
   PubMed Web of Science ®Google Scholar
• Kwan W, Wilson D, Moravan V. Radiotherapy for locally advanced basal cell and squamous cell carcinomas of the skin. Int J Radiat Oncol Biol Phys. 2004;60(2):406.
   PubMed Web of Science ®Google Scholar
• Telfer NR, Colver GB, Morton CA. British Association of Dermatologists. Guidelines for the management of basal cell carcinoma. Br J Dermatol. 2008;159:35–48.
   PubMed Web of Science ®Google Scholar
• Villani A, Costa C, Cappello M, et al. The effectiveness of vismodegib in patients with advanced periocular basal cell carcinoma: a case series of 13 patients [published online ahead of print, 2020 Jun 1]. J Dermatolog Treat. 2020;1–2. DOI:https://doi.org/10.1080/09546634.2020.1771262
   Google Scholar
• Hou X, Rokohl AC, Ortmann M, et al. Effective treatment of locally advanced periocular basal cell carcinoma with oral hedgehog pathway inhibitor? Graefes Arch Clin Exp Ophthalmol. 2020 Jun 9;258:2335–2337. Epub ahead of print. PMID: 32514773.
   Web of Science ®Google Scholar
• Silapunt S, Chen L, Migden MR. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness. Ther Adv Med Oncol. 2016;8:375–382.
   PubMed Web of Science ®Google Scholar
• Amakye D, Jagani Z, Dorsch M. Unraveling the therapeutic potential of the Hedgehog pathway in cancer. Nat Med. 2013;19(11):1410–1422.
   PubMed Web of Science ®Google Scholar
• Villani A, Fabbrocini G, Costa C, et al. Merkel cell carcinoma: therapeutic update and emerging therapies. Dermatol Ther (Heidelb). 2019;9(2):209–222.
   PubMed Web of Science ®Google Scholar
• Genentech. Erivedge_ (vismodegib) capsules, for oral use: US pre-scribing information. 2015 cited 2016 Jan 13. Available from: https://www.erivedge.com/
   Google Scholar
• Novartis. Odomzo_ (sonidegib) capsules, for oral use: US prescribing information. 2015 cited 2015 Jan 13. Available from: www.odomzo.com/
   Google Scholar
• European Medicines Agency. Erivedge 150 mg hard capsules: summary of product characteristics. 2015 cited 2016 Jan 13. Available from: https://www.ema.europa.eu/
   Google Scholar
• European Medicines Agency. Odomzo_ 200 mg hard capsules: summary of product characteristics. 2015 cited 2016 Jan 13. Available from: https://www.ema.europa.eu/
   Google Scholar
• Dummer R, Ascierto PA, Basset-Seguin N, et al. Sonidegib and vismodegib in the treatment of patients with locally advanced basal cell carcinoma: a joint expert opinion. J Eur Acad Dermatol Venereol. 2020;34:1944–1956.
   PubMed Web of Science ®Google Scholar
• Nu¨sslein-Volhard C, Wieschaus E. Mutation’s affecting segment number and polarity in Drosophila. Nature. 1980;287:795–801.
   PubMed Web of Science ®Google Scholar
• Tang JY, So PL, Epstein EH. Novel Hedgehog pathway targets against basal cell carcinoma. Toxicol Appl Pharmacol. 2007;224:257–264.
   PubMed Web of Science ®Google Scholar
• Epstein EH. Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer. 2008;8:743–754.
   PubMed Web of Science ®Google Scholar
• Villani A, Cappello M, Costa C, et al. Advanced basal cell carcinoma treated with vismodegib: impact on the lives of patients and their families [published online ahead of print, 2020 May 16]. Clin Exp Dermatol. 2020. DOI:https://doi.org/10.1111/ced.14287
   Google Scholar
• Lo JS, Snow SN, Reizner GT, et al. Metastatic basal cell carcinoma: report of twelve cases with a review of the literature. J Am Acad Dermatol. 1991;24(5 Pt 1):715–719.
   PubMed Web of Science ®Google Scholar
• Leavitt E, Lask G, Martin S. Sonic Hedgehog pathway inhibition in the treatment of advanced basal cell carcinoma. Curr Treat Options Oncol. 2019;20(11):84. Published 2019 Nov 26.
   PubMed Web of Science ®Google Scholar
• Graham RA, Lum BL, Cheeti S, et al. Pharmacokinetics of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic solid tumors: the role of alpha-1-acid glycoprotein binding. Clin Cancer Res. 2011;17(8):2512–2520.
   PubMed Web of Science ®Google Scholar
• Lorusso PM, Jimeno A, Dy G, et al. Pharmacokinetic dose-scheduling study of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with locally advanced or metastatic solid tumors. Clin Cancer Res. 2011;17(17):5774–5782.
   PubMed Web of Science ®Google Scholar
• LoRusso PM, Rudin CM, Reddy JC, et al. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res. 2011;17(8):2502–2511.
   PubMed Web of Science ®Google Scholar
• Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366:2171–2179.
   PubMed Web of Science ®Google Scholar
• Sekulic A, Schadendorf D, Solomon J, et al. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma (aBCC): 24-month update of the pivotal ERIVANCE BCC study. J Am Acad Dermatol. 2014;70(5):AB137.
   Web of Science ®Google Scholar
• Chang AL, Solomon JA, Hainsworth JD, et al. Expanded access study of patients with advanced basal cell carcinoma treated with the hedgehog pathway inhibitor, Vismodegib. J Am Acad Dermatol. 2014;70(1):60–69.
   PubMed Web of Science ®Google Scholar
• 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;366:2180–2188.
   PubMed Web of Science ®Google Scholar
• Villani A, Megna M, Fabbrocini G, et al. Long-term efficacy of vismodegib after its withdrawal and patients’ health-related quality of life using the Dermatology Life Quality Index (DLQI). Dermatol Ther (Heidelb). 2019;9(4):719–724.
   PubMed Web of Science ®Google Scholar
• Basset-Séguin N, Hauschild A, Kunstfeld R, et al. Vismodegib in patients with advanced basal cell carcinoma: primary analysis of STEVIE, an international, open-label trial. Eur J Cancer. 2017;86:334–348.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Fosko SW, Chu MB, Armbrecht E, et al. Efficacy, rate of tumor response, and safety of a short course (12–24 weeks) of oral vismodegib in various histologic subtypes (infiltrative, nodular, and superficial) of high-risk or locally advanced basal cell carcinoma, in an open-label, prospective case series clinical trial. J Am Acad Dermatol. 2020 Apr;82(4):946–954. Epub 2019 Dec 10. PMID: 31836564.
   PubMed Web of Science ®Google Scholar
• Edwards BJ, Raisch DW, Saraykar SS, et al. Hepatotoxicity with vismodegib: an MD Anderson Cancer Center and research on adverse drug events and reports Project. Drugs R D. 2017 Mar;17(1):211–218. PMID: 28063021; PMCID: PMC5318336.
   PubMed Web of Science ®Google Scholar
• Villani A, Fabbrocini G, Costa C, et al. Sonidegib: safety and efficacy in treatment of advanced basal cell carcinoma. Dermatol Ther (Heidelb). 2020;10(3):401–412.
   PubMed Web of Science ®Google Scholar
• Zollinger M, Lozac’h F, Hurh E, et al. Absorption, distribution, metabolism, and excretion (ADME) of (1)(4)C-sonidegib (LDE225) in healthy volunteers. Cancer Chemother Pharmacol. 2014;74(1):63–75.
   PubMed Web of Science ®Google Scholar
• Goel V, Hurh E, Stein A, et al. Population pharmacokinetics of sonidegib (LDE225), an oral inhibitor of hedgehog pathway signaling, in healthy subjects and in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016;77(4):745–755.
   PubMed Web of Science ®Google Scholar
• Rodon J, Tawbi HA, Thomas AL, et al. A phase I, multicenter, open-label, first-in-human, dose-escalation study of the oral smoothened inhibitor sonidegib (LDE225) in patients with advanced solid tumors. Clin Cancer Res. 2014;20(7):1900–1909.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Chen L, Silapunt S, Migden MR. Sonidegib for the treatment of advanced basal cell carcinoma: a comprehensive review of sonidegib and the BOLT trial with 12-month update. Future Oncol. 2016;12(18):2095–2105.
   PubMed Web of Science ®Google Scholar
• Lear J, Guminski A, Gutzmer R A phase 2, randomized, double-blind study of sonidegib (LDE225) in patients with advanced basal cell carcinoma: the BOLT 18-month analysis [abstract Lear J, Guminski A, Gutzmer R A phase 2, randomized, double-blind study of sonidegib (LDE225) in patients with advanced basal cell carcinoma: the BOLT 18-month analysis [abstract]. In: 24th EADV congress, Copenaghen,  Denmark; 2015.
   Google Scholar
• Lear JT, Migden MR, Lewis KD, et al. Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study. J Eur Acad Dermatol Venereol. 2018;32(3):372–381.
   PubMed Web of Science ®Google Scholar
• Dummer R, Guminksi A, Gutzmer R, et al. Longterm efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase II randomized, double-blind BOLT study. Br J Dermatol. 2019. DOI:https://doi.org/10.1111/bjd.18552.
   Google Scholar
• Horsmans Y, Zhou J, Liudmila M. Effects of mild to severe hepatic impairment on the pharmacokinetics of sonidegib: a multicenter, open-label parallel group study. Clin Pharmacokinet. 2018;57(3):345–354.
   PubMed Web of Science ®Google Scholar
• Zhou J, Quinlan M, Glenn K. Effect of esomeprazole, a proton pump inhibitor on the pharmacokinetics of sonidegib in healthy volunteers. Br J Clin Pharmacol. 2016;82(4):1022–1029.
   PubMed Web of Science ®Google Scholar
• Lear JT, Hauschild A, Stockfleth E, et al. Efficacy and safety of sonidegib in adult patients with nevoid basal cell carcinoma syndrome (gorlin syndrome): results from a phase 2, double-blind randomized trial. Clin Cosmet Investig Dermatol. 2020;13:117–121.
   PubMed Web of Science ®Google Scholar
• Ramelyte E, Amann VC, Dummer R. Sonidegib for the treatment of advanced basal cell carcinoma. Expert Opin Pharmacother. 2016;17(14):1963–1968.
   PubMed Web of Science ®Google Scholar
• Epstein EH, Lear J, Saldanha G, et al. Hedgehog pathway inhibition by topical patidegib to reduce BCC burden in patients with basal cell nevus (Gorlin) syndrome. J Clin Oncol. 2018;36:e21626–e21626.
   Web of Science ®Google Scholar
• Chen B, Trang V, Lee A, et al. Posaconazole, a second-generation triazole antifungal drug, inhibits the hedgehog signaling pathway and progression of basal cell carcinoma. Mol Cancer Ther. 2016;15:866–876.
   PubMed Web of Science ®Google Scholar
• Sohn GK, Kwon GP, Bailey-Healy I, et al. Topical itraconazole for the treatment of basal cell carcinoma in patients with basal cell nevus syndrome or high-frequency basal cell carcinomas: a phase 2, open-label, placebo-controlled trial. JAMA Dermatol. 2019;155:1078.
   PubMed Web of Science ®Google Scholar
• Kim DJ, Kim J, Spaunhurst K, et al. Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma. J Clin Oncol. 2014;32:745–751.
   PubMed Web of Science ®Google Scholar
• Lacouture ME, Dre´no B, Ascierto PA, et al. Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma. Oncologist. 2016;21(10):1218–1229.
   PubMed Web of Science ®Google Scholar
• Cozzani R, Del Aguila R, Carrizo M, et al. ML29740 investigators. Efficacy and safety profile of vismodegib in a real-world setting cohort of patients with advanced basal cell carcinoma in Argentina. Int J Dermatol. 2020;59(5):627–632.
   PubMed Web of Science ®Google Scholar
• Dinehart MS, McMurray S, Dinehart SM, et al. L-Carnitine reduces muscle cramps in patients taking vismodegib. SKIN J Cutaneous Med. 2018 Mar;2(2):90.
   Google Scholar
• Scalvenzi M, Costa C, Cappello M, et al. Managing adverse effects by dose reduction during routine treatment of locally advanced basal cell carcinoma with the hedgehog inhibitor vismodegib: a single-centre experience. J Eur Acad Dermatol Venereol. 2019;33(4):e145–e147.
   PubMed Web of Science ®Google Scholar
• Collier NJ, Ali FR, Lear JT. The safety and efficacy of sonidegib for the treatment of locally advanced basal cell carcinoma. Expert Rev Anticancer Ther. 2016;16(10):1011–1018.
   PubMed Web of Science ®Google Scholar
• Carpenter RL, Ray H. Safety and tolerability of sonic hedgehog pathway inhibitors in cancer. Drug Saf. 2019;42(2):263–279.
   PubMed Web of Science ®Google Scholar
• Villani A, Costa C, Fabbrocini G, et al. Drug holiday regimen for vismodegib treatment in patients with multiple primary basal cell carcinomas [published online ahead of print, 2020 May 30]. Dermatol Ther. 2020;e13707. DOI:https://doi.org/10.1111/dth.13707
   Google Scholar
• Scalvenzi M, Villani A, Mazzella C, et al. Vismodegib treatment in a HIV positive patient on antiretroviral therapy. Indian J Dermatol Venereol Leprol. 2018;84(6):758–760.
   PubMed Web of Science ®Google Scholar