Emerging drugs and combination strategies for basal cell carcinoma

Abstract

Introduction: Basal cell carcinoma (BCC) is a malignancy that is driven by an activated Hedgehog (Hh) pathway. Smoothened inhibitors are a new promising treatment option for patients with locally advanced or metastatic BCC or basal cell nevus syndrome. But long-term data are still limited, the optimal treatment duration is not yet defined and there are already documented cases with acquired resistance.

Areas covered: Treatment modalities with Hh inhibitors, side effects and potential pharmacological combination options are discussed. The current literature, including PubMed, Cochrane database and registered trials on ClinicalTrials.gov, was searched.

Expert opinion: BCCs typically regress during therapy with Hh inhibitors. Muscle toxicity, dysgeusia and hair loss can be considered as on target adverse reactions. Muscle toxicity is the dose-limiting toxicity of sonidegib. It was not seen with vismodegib because of its high binding to plasma protein α-1-acid glycoprotein. Sonidegib is different and shows a clear dose–toxicity relationship, which allows to address the question of whether there is a dose dependency of regression rate, cure rate and progression-free survival. In addition, basic research has offered strategies to enhance efficacy by the combination with other molecules, such as EGFR inhibitors, MEK inhibitors or immunotherapy.

Keywords::

• adverse events
• basal cell carcinoma
• combination therapy
• Hedgehog inhibitors
• resistance
• side effects
• smoothened inhibitors
• sonidegib
• toxic myopathy

Acknowledgment

J Dreier and R Dummer have equally contributed to this work. The authors would like to thank Margit Hemetsberger of Hemetsberger medical services, Vienna, Austria, for her help in editing this manuscript.

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