Keratinocyte cancers–basal and cutaneous squamous cell carcinoma (BCC, cSCC)–are the most common forms of non-melanoma skin cancer and there has been a significant increase in their incidence globally in recent decades. Although the majority of BCC and cSCC are cured with conventional surgery or radiotherapy, certain tumour or patient-determined factors may result in these modalities being inadequate or inappropriate, for example, locally advanced or metastatic disease, high tumour multiplicity, patient comorbidities and patient preferences. Pathobiologically, activation of the Hedgehog (HH) signalling pathway has been shown to play a critical role in the majority of cases and is recognised as a valid therapeutic target. As such, hedgehog pathway inhibitors such as vismodegib and sonidegib are being investigated in high-risk cancers.
Vismodegib is a small-molecule inhibitor of smoothened (SMO), a key component of the hedgehog signalling pathway that has been studied in BCC patients after failure of surgery and radiotherapy treatments. 
Vismodegib has become an established treatment option for patients with advanced BCC in clinical practice.
However, certain limitations of treatment with vismodegib should be kept in mind.
Side effects lead to a significant rate of treatment discontinuation, thereby limiting overall drug exposure.
Accordingly, continuous long-term treatment with vismodegib is not feasible in most patients.
Clinical end points which may help to determine the optimal treatment duration (lifelong/continuous treatment vs treatment until best response) are lacking.
Alternative dosing regimens may improve tolerability and dose exposure, but more studies are needed to optimise the dosing regimen. 
Muscle cramps are an important side effect of vismodegib, but may be reduced with the administration of L-carnitine, based on a case report. 
Other side effects include decreased sense of taste, hair loss, loss of appetite, weight loss and fatigue, as well as severe birth defects.
Of note, it has been reported that in advanced BCC, patients who are resistant to treatment with vismodegib are also resistant to sonidegib. 
Sekulic A, Migden MR2, Basset-Seguin N, et al. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. BMC Cancer. 2017 May 16;17(1):332.
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 Mar;18(3):404-12.
Dinehart MS, McMurray, S, Dinehart S, et al. L-Carnitine reduces muscle cramps in patients taking vismodegib. Skin. 2018;2:2.
Presented by: Prof. Kristian Reich, Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, and Skinflammation® Center, Hamburg, Germany