Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma

Mario E. Lacouture, Brigitte Dréno, Paolo Antonio Ascierto, Reinhard Dummer, Nicole Basset-Seguin, Kate Fife, Scott Ernst, Lisa Licitra, Rogerio I. Neves, Ketty Peris, Susana Puig, Jonas Sokolof, Aleksandar Sekulic, Axel Hauschild, Rainer Kunstfeld

Research output: Contribution to journalArticle

58 Scopus citations

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 bemechanistically 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-termnature 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.

Original languageEnglish (US)
Pages (from-to)1218-1229
Number of pages12
JournalOncologist
Volume21
Issue number10
DOIs
StatePublished - Oct 2016

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma'. Together they form a unique fingerprint.

  • Cite this

    Lacouture, M. E., Dréno, B., Ascierto, P. A., Dummer, R., Basset-Seguin, N., Fife, K., Ernst, S., Licitra, L., Neves, R. I., Peris, K., Puig, S., Sokolof, J., Sekulic, A., Hauschild, A., & Kunstfeld, R. (2016). Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma. Oncologist, 21(10), 1218-1229. https://doi.org/10.1634/theoncologist.2016-0186