Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Dummer, R.
Guminski, A.
Gutzmer, R.
Dirix, L.
Lewis, K.D.
Combemale, P.
Herd, R.M.
Kaatz, M.
Loquai, C.
Stratigos, A.J.
Schulze, H.-J.
Plummer, R.
Gogov, S.
Pallaud, C.
Yi, T.
Mone, M.
Chang, A.L.S.
Cornélis, F.
Kudchadkar, R.
Trefzer, U.
Lear, J.T.
Sellami, D.
Migden, M.R.
Περιοδικό:
Journal of the American Academy of Dermatology
Εκδότης:
Mosby Year Book Inc
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.jaad.2016.02.1226
