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 D Sekulic, Axel Hauschild, Rainer Kunstfeld

Research output: Contribution to journalArticle

47 Citations (Scopus)

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 1 2016

Fingerprint

Basal Cell Carcinoma
HhAntag691
Ageusia
Dysgeusia
Quality of Life
Asthenia
Alopecia
Spasm
Fatigue
Counseling
Weight Loss
Therapeutics
Radiation
Delivery of Health Care
Incidence

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lacouture, M. E., Dréno, B., Ascierto, P. A., Dummer, R., Basset-Seguin, N., Fife, K., ... 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

Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma. / Lacouture, Mario E.; Dréno, Brigitte; Ascierto, Paolo Antonio; Dummer, Reinhard; Basset-Seguin, Nicole; Fife, Kate; Ernst, Scott; Licitra, Lisa; Neves, Rogerio I.; Peris, Ketty; Puig, Susana; Sokolof, Jonas; Sekulic, Aleksandar D; Hauschild, Axel; Kunstfeld, Rainer.

In: Oncologist, Vol. 21, No. 10, 01.10.2016, p. 1218-1229.

Research output: Contribution to journalArticle

Lacouture, ME, Dréno, B, Ascierto, PA, Dummer, R, Basset-Seguin, N, Fife, K, Ernst, S, Licitra, L, Neves, RI, Peris, K, Puig, S, Sokolof, J, Sekulic, AD, Hauschild, A & Kunstfeld, R 2016, 'Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma', Oncologist, vol. 21, no. 10, pp. 1218-1229. https://doi.org/10.1634/theoncologist.2016-0186
Lacouture, Mario E. ; Dréno, Brigitte ; Ascierto, Paolo Antonio ; Dummer, Reinhard ; Basset-Seguin, Nicole ; Fife, Kate ; Ernst, Scott ; Licitra, Lisa ; Neves, Rogerio I. ; Peris, Ketty ; Puig, Susana ; Sokolof, Jonas ; Sekulic, Aleksandar D ; Hauschild, Axel ; Kunstfeld, Rainer. / Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma. In: Oncologist. 2016 ; Vol. 21, No. 10. pp. 1218-1229.
@article{d74e79e6448346679ff188b1f597fb0c,
title = "Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma",
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.",
keywords = "Advanced basal cell carcinoma, Adverse events, Hedgehog pathway, Management, Sonidegib, Vismodegib",
author = "Lacouture, {Mario E.} and Brigitte Dr{\'e}no and Ascierto, {Paolo Antonio} and Reinhard Dummer and Nicole Basset-Seguin and Kate Fife and Scott Ernst and Lisa Licitra and Neves, {Rogerio I.} and Ketty Peris and Susana Puig and Jonas Sokolof and Sekulic, {Aleksandar D} and Axel Hauschild and Rainer Kunstfeld",
year = "2016",
month = "10",
day = "1",
doi = "10.1634/theoncologist.2016-0186",
language = "English (US)",
volume = "21",
pages = "1218--1229",
journal = "Oncologist",
issn = "1083-7159",
publisher = "AlphaMed Press",
number = "10",

}

TY - JOUR

T1 - Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma

AU - Lacouture, Mario E.

AU - Dréno, Brigitte

AU - Ascierto, Paolo Antonio

AU - Dummer, Reinhard

AU - Basset-Seguin, Nicole

AU - Fife, Kate

AU - Ernst, Scott

AU - Licitra, Lisa

AU - Neves, Rogerio I.

AU - Peris, Ketty

AU - Puig, Susana

AU - Sokolof, Jonas

AU - Sekulic, Aleksandar D

AU - Hauschild, Axel

AU - Kunstfeld, Rainer

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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.

AB - 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.

KW - Advanced basal cell carcinoma

KW - Adverse events

KW - Hedgehog pathway

KW - Management

KW - Sonidegib

KW - Vismodegib

UR - http://www.scopus.com/inward/record.url?scp=84991734849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991734849&partnerID=8YFLogxK

U2 - 10.1634/theoncologist.2016-0186

DO - 10.1634/theoncologist.2016-0186

M3 - Article

VL - 21

SP - 1218

EP - 1229

JO - Oncologist

JF - Oncologist

SN - 1083-7159

IS - 10

ER -