Long-term efﬁcacy and safety of sonidegib in patients with
locally advanced and metastatic basal cell carcinoma:
30-month analysis of the randomized phase 2 BOLT study
* M.R. Migden,
Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
Departments of Dermatology and Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, USA
Stanford University School of Medicine, Redwood City, CA, USA
Royal North Shore Hospital, St Leonards, NSW, Australia
Medizinische Hochschule Hannover, Hannover, Germany
Sint-Augustinus Ziekenhuis, Antwerp, Belgium
Anti Cancer Institute, L
erard, Lyon, France
Andreas Syggros Hospital, University of Athens, Athens, Greece
Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, UK
Novartis Pharma AG, Basel, Switzerland
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
Dermatologikum Berlin, Berlin, Germany
University Hospital Jena, Jena, Germany
University Medical Center Mainz, Mainz, Germany
Winship Cancer Institute of Emory University, Atlanta, GA, USA
urich-Skin Cancer Center, University Hospital, Z
*Correspondence: J.T. Lear. E-mail: email@example.com
Background Patients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC), two difﬁcult-to-
treat populations, have had limited treatment options. Sonidegib, a hedgehog pathway inhibitor (HPI), was approved in
laBCC based on results from the BOLT trial.
Objective To evaluate long-term efﬁcacy and safety of sonidegib in laBCC and mBCC in the BOLT 18- and 30-month
Methods BOLT (NCT01327053, ClinicalTrials.gov), a double-blind phase 2 study, enrolled patients from July 2011 until
January 2013. Eligible HPI-treatment–na
ıve patients with laBCC not amenable to curative surgery/radiotherapy or mBCC
were randomized 1 : 2 to sonidegib 200 mg (laBCC, n = 66; mBCC, n = 13) or 800 mg (laBCC, n = 128; mBCC,
n = 23). Tumour response was assessed per central and investigator review.
Results With 30 months of follow-up, among patients treated with sonidegib 200 mg (approved dose), objective
response rates were 56.1% (central) and 71.2% (investigator) in laBCC and 7.7% (central) and 23.1% (investigator) in
mBCC. Tumour responses were durable as follows: median duration of response was 26.1 months (central) and
15.7 months (investigator) in laBCC and 24.0 months (central) and 18.1 months (investigator) in mBCC. Five patients
with laBCC and three with mBCC in the 200-mg arm died. Median overall survival was not reached in either population;
2-year overall survival rates were 93.2% (laBCC) and 69.3% (mBCC). In laBCC, efﬁcacy was similar regardless of
aggressive or non-aggressive histology. Sonidegib 200 mg continued to have a better safety proﬁle than 800 mg, with
lower rates of grade 3/4 adverse events (43.0% vs. 64.0%) and adverse events leading to discontinuation (30.4% vs.
†Afﬁliation at the time the study was conducted. HC and TY are no longer
afﬁliated with Novartis Pharmaceuticals.
© 2017 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd
on behalf of European Academy of Dermatology and Venereology.
2018, 32, 372–381
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