The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma.

Autor: Dummer R; UniversitätsSpital Zürich-Skin Cancer Center, University Hospital, Zürich, Switzerland. Electronic address: reinhard.dummer@usz.ch., Guminski A; Royal North Shore Hospital, Sydney, Australia., Gutzmer R; Medizinische Hochschule Hannover, Hannover, Germany., Dirix L; Sint-Augustinus Ziekenhuis, Antwerp, Belgium., Lewis KD; Division of Medical Oncology, School of Medicine, University of Colorado, Aurora, Colorado., Combemale P; Anti Cancer Institute, Léon Bérard, Lyon, France., Herd RM; Glasgow Royal Infirmary, Glasgow, United Kingdom., Kaatz M; University Hospital Jena, Jena, Germany; SRH Wald-Klinikum Gera GmbH, Gera, Germany., Loquai C; University Medical Center Mainz, Mainz, Germany., Stratigos AJ; Department of Dermatology, Andreas Sygros Hospital, University of Athens, Athens, Greece., Schulze HJ; Fachklinik Hornheide, Münster, Germany., Plummer R; Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, United Kingdom., Gogov S; Novartis Pharma AG, Oncology Global Development, Basel, Switzerland., Pallaud C; Novartis Pharma AG, Oncology Global Development, Basel, Switzerland., Yi T; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey., Mone M; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey., Chang AL; Stanford University School of Medicine, Redwood City, California., Cornélis F; Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium., Kudchadkar R; Winship Cancer Institute at Emory University, Atlanta, Georgia., Trefzer U; Dermatologikum Berlin, Berlin, Germany., Lear JT; Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom., Sellami D; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey., Migden MR; Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas.
Jazyk: angličtina
Zdroj: Journal of the American Academy of Dermatology [J Am Acad Dermatol] 2016 Jul; Vol. 75 (1), pp. 113-125.e5. Date of Electronic Publication: 2016 Apr 07.
DOI: 10.1016/j.jaad.2016.02.1226
Abstrakt: Background: The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study.
Objective: This report provides long-term follow-up data collected up to 12 months after the last patient was randomized.
Methods: In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review.
Results: Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively).
Limitations: No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved.
Conclusion: With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC.
(Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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