TY - JOUR
T1 - The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT)
T2 - A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma
AU - Dummer, Reinhard
AU - Guminski, Alexander
AU - Gutzmer, Ralf
AU - Dirix, Luc
AU - Lewis, Karl D.
AU - Combemale, Patrick
AU - Herd, Robert M.
AU - Kaatz, Martin
AU - Loquai, Carmen
AU - Stratigos, Alexander J.
AU - Schulze, Hans Joachim
AU - Plummer, Ruth
AU - Gogov, Sven
AU - Pallaud, Celine
AU - Yi, Tingting
AU - Mone, Manisha
AU - Chang, Anne Lynn S.
AU - Cornélis, Frank
AU - Kudchadkar, Ragini
AU - Trefzer, Uwe
AU - Lear, John T.
AU - Sellami, Dalila
AU - Migden, Michael R.
N1 - Publisher Copyright:
© 2016 American Academy of Dermatology, Inc.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
KW - Advanced basal cell carcinoma
KW - Basal Cell Carcinoma Outcomes with LDE225 Treatment study
KW - Hedgehog pathway inhibitor
KW - Locally advanced basal cell carcinoma
KW - Metastatic basal cell carcinoma
KW - Sonidegib
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U2 - 10.1016/j.jaad.2016.02.1226
DO - 10.1016/j.jaad.2016.02.1226
M3 - Article
C2 - 27067394
AN - SCOPUS:84962679495
SN - 0190-9622
VL - 75
SP - 113-125.e5
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 1
ER -