TY - JOUR
TI - 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
AU - Dummer, R.
AU - Guminski, A.
AU - Gutzmer, R.
AU - Dirix, L.
AU - Lewis, K.D.
AU - Combemale, P.
AU - Herd, R.M.
AU - Kaatz, M.
AU - Loquai, C.
AU - Stratigos, A.J.
AU - Schulze, H.-J.
AU - Plummer, R.
AU - Gogov, S.
AU - Pallaud, C.
AU - Yi, T.
AU - Mone, M.
AU - Chang, A.L.S.
AU - Cornélis, F.
AU - Kudchadkar, R.
AU - Trefzer, U.
AU - Lear, J.T.
AU - Sellami, D.
AU - Migden, M.R.
JO - Journal of the American Academy of Dermatology
PY - 2016
VL - 75
TODO - 1
SP - 113-125.e5
PB - Mosby Year Book Inc
SN - 0190-9622, 1097-6787
TODO - 10.1016/j.jaad.2016.02.1226
TODO - creatine kinase;  sonidegib;  vismodegib;  antineoplastic agent;  biphenyl derivative;  pyridine derivative;  Smoothened protein;  sonidegib, adult;  advanced cancer;  alopecia;  Article;  basal cell carcinoma;  cancer patient;  controlled study;  creatine kinase blood level;  decreased appetite;  diarrhea;  double blind procedure;  drug efficacy;  drug safety;  drug withdrawal;  dysgeusia;  fatigue;  female;  follow up;  human;  major clinical study;  male;  multicenter study;  muscle spasm;  myalgia;  nausea;  outcome assessment;  phase 1 clinical trial;  phase 2 clinical trial;  priority journal;  randomized controlled trial;  rhabdomyolysis;  side effect;  treatment response;  vomiting;  weight reduction;  aged;  antagonists and inhibitors;  Carcinoma, Basal Cell;  clinical trial;  disease course;  middle aged;  pathology;  secondary;  Skin Neoplasms;  survival rate;  very elderly;  young adult, Adult;  Aged;  Aged, 80 and over;  Antineoplastic Agents;  Biphenyl Compounds;  Carcinoma, Basal Cell;  Disease Progression;  Double-Blind Method;  Female;  Humans;  Male;  Middle Aged;  Pyridines;  Skin Neoplasms;  Smoothened Receptor;  Survival Rate;  Young Adult
TODO - 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. © 2016 American Academy of Dermatology, Inc.
ER -