TY - JOUR
T1 - Effects of Sonidegib Following Dose Reduction and Treatment Interruption in Patients with Advanced Basal Cell Carcinoma During 42-Month BOLT Trial
AU - Lewis, Karl
AU - Dummer, Reinhard
AU - Farberg, Aaron S.
AU - Guminski, Alexander
AU - Squittieri, Nicholas
AU - Migden, Michael
N1 - Funding Information:
This study was sponsored and funded by Novartis. The journal’s rapid service fee was funded by Sun Pharmaceutical Industries, Inc. (Princeton, NJ, USA). Writing and editorial support for manuscript preparation were provided by Zehra Gundogan, VMD, of AlphaBioCom, LLC, and funded by Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA.
Funding Information:
This study was sponsored and funded by Novartis. The journal?s rapid service fee was funded by Sun Pharmaceutical Industries, Inc. (Princeton, NJ, USA). Writing and editorial support for manuscript preparation were provided by Zehra Gundogan, VMD, of AlphaBioCom, LLC, and funded by Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA. All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors and have significantly contributed to, seen, and approved the final submitted version of the manuscript. KL, RD, ASF, AG, NS, and MM drafted and critically reviewed the manuscript and approved the final version. Medical writing and editorial assistance were provided by Zehra Gundogan, VMD, of AlphaBioCom, LLC, under the direction of the authors and was funded by Sun Pharmaceutical Industries, Inc. Karl Lewis has received grants and personal fees from Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, and Roche. Reinhard Dummer has participated on advisory boards and consulted for Amgen; Bristol-Myers Squibb; Catalym; Merck Sharpe & Dohme; Novartis Pharmaceutical Corporation; Pierre Fabre; Roche; Sanofi; Second Genome; Sun Pharmaceutical Industries, Inc.; and Takeda. Aaron S. Farberg has participated on advisory boards and received honoraria from Ortho Dermatologics and Sun Pharmaceutical Industries, Inc. Alexander Guminski has participated on advisory boards for Bristol-Myers Squibb, Pfizer, and Sanofi; received honoraria from Novartis; and received travel support from Astellas; Bristol-Myers Squibb; and Sun Pharmaceutical Industries, Inc. Nicholas Squittieri is an employee of Sun Pharmaceutical Industries, Inc. Michael Migden has participated on advisory boards and received honoraria from Genentech; Novartis; Sun Pharmaceutical Industries, Inc.; and Regeneron. This study was conducted according to the ethical principles of the Declaration of Helsinki. All patients provided informed consent for publication of this report. The study protocol and all amendments were approved by the institutional review board/independent ethics committee for each center (Table S1 in the supplementary material). All data generated or analyzed during this study are included in this published article/as supplementary information files.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Introduction: Sonidegib is a Hedgehog pathway inhibitor approved to treat locally advanced basal cell carcinoma and, depending on regulatory approval, metastatic basal cell carcinoma. Results from the BOLT study demonstrated robust efficacy and continued tolerability through 42 months. This analysis evaluated the impact of sonidegib dose reductions and interruptions in patients with advanced basal cell carcinoma through 42 months. Methods: BOLT was a randomized, double-blind, multicenter, phase 2 study. Adults with no previous Hedgehog pathway inhibitor therapy were randomized 1:2 to sonidegib 200 or 800 mg once daily. Primary endpoint was objective response rate. Dose modifications were permitted in patients unable to tolerate the dosing schedule or if a treatment-related adverse event was suspected. Results: The incidence of dose interruptions was similar between the 200- and 800-mg groups (68.4% vs 65.3%, respectively). Dose reductions occurred more frequently in patients receiving sonidegib 800 mg (36.7%) than 200 mg (16.5%). Overall response rate for all patients receiving sonidegib 200 mg daily was 48.1% and was similar to those of patients without dose reduction or interruption (48.5%) and patients with at least one dose reduction or interruption (46.2%). Conclusion: Dose reductions and interruptions were practical and did not impact the efficacy of sonidegib. In patients with advanced basal cell carcinoma who necessitate long-term treatment, dose interruptions may be beneficial for continued treatment and disease control. Trial registration: ClinicalTrials.gov identifier, NCT01327053.
AB - Introduction: Sonidegib is a Hedgehog pathway inhibitor approved to treat locally advanced basal cell carcinoma and, depending on regulatory approval, metastatic basal cell carcinoma. Results from the BOLT study demonstrated robust efficacy and continued tolerability through 42 months. This analysis evaluated the impact of sonidegib dose reductions and interruptions in patients with advanced basal cell carcinoma through 42 months. Methods: BOLT was a randomized, double-blind, multicenter, phase 2 study. Adults with no previous Hedgehog pathway inhibitor therapy were randomized 1:2 to sonidegib 200 or 800 mg once daily. Primary endpoint was objective response rate. Dose modifications were permitted in patients unable to tolerate the dosing schedule or if a treatment-related adverse event was suspected. Results: The incidence of dose interruptions was similar between the 200- and 800-mg groups (68.4% vs 65.3%, respectively). Dose reductions occurred more frequently in patients receiving sonidegib 800 mg (36.7%) than 200 mg (16.5%). Overall response rate for all patients receiving sonidegib 200 mg daily was 48.1% and was similar to those of patients without dose reduction or interruption (48.5%) and patients with at least one dose reduction or interruption (46.2%). Conclusion: Dose reductions and interruptions were practical and did not impact the efficacy of sonidegib. In patients with advanced basal cell carcinoma who necessitate long-term treatment, dose interruptions may be beneficial for continued treatment and disease control. Trial registration: ClinicalTrials.gov identifier, NCT01327053.
KW - Basal cell carcinoma
KW - Dose interruption
KW - Dose reduction
KW - Hedgehog pathway inhibitor
KW - Sonidegib
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U2 - 10.1007/s13555-021-00619-4
DO - 10.1007/s13555-021-00619-4
M3 - Article
C2 - 34669179
AN - SCOPUS:85117382446
SN - 2193-8210
VL - 11
SP - 2225
EP - 2234
JO - Dermatology and Therapy
JF - Dermatology and Therapy
IS - 6
ER -