Oncotarget

Research Papers:

Expression of Glioma-associated oncogene homolog 1 as biomarker with sonidegib in advanced basal cell carcinoma

Reinhard Dummer _, Li Liu, Nicholas Squittieri, Ralf Gutzmer and John Lear

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Oncotarget. 2020; 11:3473-3483. https://doi.org/10.18632/oncotarget.27735

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Abstract

Reinhard Dummer1, Li Liu2, Nicholas Squittieri2, Ralf Gutzmer3 and John Lear4

1 Department of Dermatology, University of Zürich, Skin Cancer Center, University Hospital, Zürich, Switzerland

2 Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA

3 Skin Cancer Center Hannover, Department of Dermatology, Hannover Medical School, Hannover, Germany

4 Manchester Academic Health Science Centre, Manchester University and Salford Royal NHS Trust, Manchester, UK

Correspondence to:

Reinhard Dummer,email: reinhard.dummer@usz.ch

Keywords: biomarker; Glioma-associated oncogene homolog 1; basal cell carcinoma; Hedgehog pathway inhibitor; sonidegib

Received: May 27, 2020     Accepted: August 17, 2020     Published: September 15, 2020

ABSTRACT

The pivotal BOLT (Basal cell carcinoma Outcomes with LDE225 [sonidegib] Treatment) study established the durable efficacy and manageable toxicity of sonidegib 200 mg once daily (QD) through 42 months in patients with advanced basal cell carcinoma (BCC). This secondary analysis used expression of Glioma-associated oncogene homolog 1 (GLI1) as a biomarker to assess the extent of Hedgehog pathway inhibition by sonidegib in patients with locally advanced BCC (laBCC) and metastatic BCC (mBCC). The study enrolled 230 patients, 79 and 151 receiving sonidegib 200 and 800 mg QD, respectively. At week 17, GLI1 expression was reduced from baseline by a median percentage (95% confidence interval) of 88.7% (54.6%–93.0%) and 97.0% (77.5%–98.9%) for aggressive laBCC, 97.5% (80.3%–98.8%) and 95.0% (80.7%–97.5%) for nonaggressive laBCC, and 99.1% (96.4%–99.6%) and 99.3% (95.9%–99.9%) for mBCC in the 200 and 800 mg groups, respectively. Substantial repression of GLI1 was observed in patient subgroups stratified by age, sex, BCC cytological subtype, Eastern Cooperative Oncology Group performance status, lesion site, baseline number of BCCs, and prior radiotherapy. Results support further studies on the inhibition of Hedgehog pathway genes by sonidegib in patients with laBCC and mBCC.


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