Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2016

Open Access 01-12-2016 | Research

Safety and efficacy of vismodegib in patients with basal cell carcinoma nevus syndrome: pooled analysis of two trials

Authors: Anne Lynn S. Chang, Sarah T. Arron, Michael R. Migden, James A. Solomon, Simon Yoo, Bann-Mo Day, Edward F. McKenna, Aleksandar Sekulic

Published in: Orphanet Journal of Rare Diseases | Issue 1/2016

Login to get access

Abstract

Background

Aberrant activation of the Hedgehog (Hh) pathway is a key driver in the pathogenesis of basal cell carcinomas (BCCs), including patients with BCC nevus syndrome (BCCNS). It is unclear whether BCCs arising in patients with BCCNS respond differently to vismodegib than in patients without BCCNS. We examined the best overall response rate (BORR) and adverse events (AEs) of vismodegib in patients with advanced BCC (aBCC) with and without BCCNS.

Methods

Patients were treated with vismodegib 150 mg/day in the ERIVANCE BCC trial (ClinicalTrials.gov number, NCT00833417) and the expanded access study (EAS; ClinicalTrials.gov number, NCT01160250). BCCNS diagnosis was based on medical history at the time of enrollment. Metastatic BCC response was evaluated using Response Evaluation Criteria In Solid Tumors, version 1.0 (RECIST v1.0) in both studies. Locally advanced BCC was evaluated by a novel composite end point in ERIVANCE BCC and by RECIST v1.0 in the EAS. Response assessments were performed every 8 weeks in ERIVANCE BCC and every 8–16 weeks in the EAS. Safety assessments (National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0) were performed monthly in both trials. Because of described differences in response assessment/schedule, patients with BCCNS were not pooled across trials. Analytic cohorts for BCCNS and sporadic aBCC were created within each trial for comparison using descriptive statistical methods.

Results

Forty-one patients with BCCNS were included in the study: 22 from ERIVANCE BCC and 19 from the EAS. Investigator-assessed BORR in BCCNS groups ranged from 31 to 81 % in patients with locally advanced BCC (n = 33) and was 50 % in patients with metastatic BCC (n = 6). These results were comparable with the non-BCCNS groups. Incidence and severity of AEs were also comparable between the BCCNS and non-BCCNS groups. Amenorrhea was observed in both patient cohorts and was reversible in two patients who discontinued treatment.

Conclusion

Vismodegib demonstrated comparable efficacy and safety against aBCC in patients with and without BCCNS.
Literature
1.
2.
Göppner D, Leverkus M. Basal cell carcinoma: from the molecular understanding of the pathogenesis to targeted therapy of progressive disease. J Skin Cancer. 2011;2011:650258.PubMed
3.
Sekulic A, Mangold AR, Northfelt DW, LoRusso PM. Advanced basal cell carcinoma of the skin: targeting the hedgehog pathway. Curr Opin Oncol. 2013;25(3):218–23.PubMed
4.
Lo Muzio L. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis. 2008;3:32.CrossRef
5.
Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171–9.CrossRefPubMed
6.
Tang JY, Kay-Wiggan JM, Aszterbaum M, Yauch RL, Lindgren J, Chang K, et al. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012;366(23):2180–8.CrossRefPubMedPubMedCentral
7.
Chang AL, Solomon JA, Hainsworth JD, Goldberg L, McKenna E, Day BM, et al. Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib. J Am Acad Dermatol. 2014;70(1):60–9.CrossRefPubMed
8.
Sekulic A, Weiss GJ, Solomon JA, Rudin CM, Guillot B, Williams S, et al. Amenorrhea or irregular menses in patients treated with vismodegib. Presented at: 2014 Winter Clinical Dermatology Conference Hawaii; Kohala Coast, Hawaii. 2014
9.
Spicer LJ, Sudo S, Aad PY, Wang LS, Chun SY, Ben-Shlomo I, et al. The hedgehog-patched signaling pathway and function in the mammalian ovary: a novel role for hedgehog proteins in stimulating proliferation and steroidogenesis of theca cells. Reproduction. 2009;138(2):329–39.CrossRefPubMed
10.
Strasswimmer J, Latimer B, Ory S. Amenorrhea secondary to a vismodegib-induced blockade of follicle-stimulating hormone-receptor activation. Fertil Steril. 2014;102(2):555–7.CrossRefPubMed
Metadata
Title
Safety and efficacy of vismodegib in patients with basal cell carcinoma nevus syndrome: pooled analysis of two trials
Authors
Anne Lynn S. Chang
Sarah T. Arron
Michael R. Migden
James A. Solomon
Simon Yoo
Bann-Mo Day
Edward F. McKenna
Aleksandar Sekulic
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2016
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-016-0506-z

Other articles of this Issue 1/2016

Orphanet Journal of Rare Diseases 1/2016 Go to the issue

Research

Gene expression profiles and protein-protein interaction networks in amyotrophic lateral sclerosis patients with C9orf72 mutation

Erratum

Erratum to: Review and evaluation of the methodological quality of the existing guidelines and recommendations for inherited neurometabolic disorders

Research

Early pancreatic volume reduction on CT predicts relapse in patients with type 1 autoimmune pancreatitis treated with steroids

Research

Thirteen year retrospective review of the spectrum of inborn errors of metabolism presenting in a tertiary center in Saudi Arabia

Research

Treatment with Oral ATP decreases alternating hemiplegia of childhood with de novo ATP1A3 Mutation

Letter to the Editor

Diffuse reduction of cerebral grey matter volumes in Erdheim-Chester disease