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Oncologist. 2016 Oct;21(10):1218-1229. Epub 2016 Aug 10.

Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma.

Author information

1
Memorial Sloan Kettering Cancer Center, New York, New York, USA LacoutuM@mskcc.org.
2
Department of Dermatology, Hôtel Dieu University Hospital, Nantes, France.
3
Istituto Nazionale Tumori Fondazione, G Pascale, Naples, Italy.
4
University of Zurich Hospital, Zurich, Switzerland.
5
Université Paris 7 and Hôpital Saint-Louis, Paris, France.
6
Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom.
7
Western University London Regional Cancer Program, London, Ontario, Canada.
8
Fondazione IRCCS, Istituto Tumori, Milan, Italy.
9
Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
10
Catholic University of Rome, Rome, Italy.
11
Dermatology Department, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomédiques August Pi I Sunyer, Barcelona, Spain.
12
Memorial Sloan Kettering Cancer Center, New York, New York, USA.
13
Mayo Clinic, Scottsdale, Arizona, USA.
14
Department of Dermatology, University of Kiel, Kiel, Germany.
15
Medical University of Vienna, Vienna, Austria.

Abstract

Abnormal activation of hedgehog pathway signaling is a key driver in the pathogenesis of basal cell carcinoma (BCC). Vismodegib, a first-in-class small-molecule inhibitor of hedgehog pathway signaling, is approved by regulatory authorities for the treatment of adults who have metastatic BCC or locally advanced BCC that has recurred after surgery, or who are not candidates for surgery and who are not candidates for radiation. A second inhibitor, sonidegib, was also recently approved for the same patient group with locally advanced BCC. Adverse events (AEs) commonly observed in hedgehog pathway inhibitor (HPI)-treated patients include muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and asthenia (fatigue). These AEs are thought to be mechanistically related to inhibition of the hedgehog pathway in normal tissue. Although the severity of the majority of AEs associated with HPIs is grade 1-2, the long-term nature of these AEs can lead to decreased quality of life, treatment interruption, and in some cases discontinuation, all of which might affect clinical outcome. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to HPIs in advanced BCC are described. These observations represent the first step toward the development of mechanism-based preventive and management strategies. Knowledge of these AEs will allow health care professionals to provide appropriate counseling and supportive care interventions, all of which will contribute to improved quality of life and optimal benefit from therapy.

IMPLICATIONS FOR PRACTICE:

The hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib represent a therapeutic breakthrough for patients with advanced basal cell carcinoma. However, the nature of the low-grade adverse events (AEs) commonly observed in HPI-treated patients, including muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and fatigue, can impact clinical outcomes as a result of decreased quality of life and treatment discontinuation. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to administration of HPIs are described, with the goal of enabling health care professionals to provide appropriate counseling and supportive care interventions to their patients.

KEYWORDS:

Advanced basal cell carcinoma; Adverse events; Hedgehog pathway; Management; Sonidegib; Vismodegib

PMID:
27511905
PMCID:
PMC5061532
DOI:
10.1634/theoncologist.2016-0186
[Indexed for MEDLINE]
Free PMC Article

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