Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study

Autor: Ruth Plummer, Martin Kaatz, Alexander Guminski, Patrick Combemale, Karl D. Lewis, Ragini R. Kudchadkar, Manisha Mone, Dalila Sellami, Jocelyn Zhou, Carmen Loquai, Luc Dirix, Anne Lynn S. Chang, Ralf Gutzmer, John T. Lear, Tingting Yi, Michael R. Migden, Reinhard Dummer, Alexandros Stratigos, Uwe Trefzer, Henry Castro
Přispěvatelé: University of Zurich, Lear, J T
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Oncology
Male
Skin Neoplasms
Pyridines
Phases of clinical research
Sonidegib
law.invention
030207 dermatology & venereal diseases
chemistry.chemical_compound
0302 clinical medicine
Randomized controlled trial
law
Original Articles and Short Reports
Medicine
Neoplasm Metastasis
education.field_of_study
10177 Dermatology Clinic
Middle Aged
Survival Rate
Infectious Diseases
Treatment Outcome
030220 oncology & carcinogenesis
Female
Original Article
Adult
medicine.medical_specialty
Population
Antineoplastic Agents
610 Medicine & health
Dermatology
2708 Dermatology
03 medical and health sciences
Double-Blind Method
Internal medicine
Humans
Basal cell carcinoma
Hedgehog Proteins
education
Survival rate
Aged
business.industry
Biphenyl Compounds
2725 Infectious Diseases
medicine.disease
Surgery
Discontinuation
Clinical trial
chemistry
Carcinoma
Basal Cell

business
Follow-Up Studies
Zdroj: Journal of the European Academy of Dermatology and Venereology
Popis: Background Patients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC), two difficult-to-treat populations, have had limited treatment options. Sonidegib, a hedgehog pathway inhibitor (HPI), was approved in laBCC based on results from the BOLT trial. Objective To evaluate long-term efficacy and safety of sonidegib in laBCC and mBCC in the BOLT 18- and 30-month analyses. Methods BOLT (NCT01327053, ClinicalTrials.gov), a double-blind phase 2 study, enrolled patients from July 2011 until January 2013. Eligible HPI-treatment–naive patients with laBCC not amenable to curative surgery/radiotherapy or mBCC were randomized 1 : 2 to sonidegib 200 mg (laBCC, n = 66; mBCC, n = 13) or 800 mg (laBCC, n = 128; mBCC, n = 23). Tumour response was assessed per central and investigator review. Results With 30 months of follow-up, among patients treated with sonidegib 200 mg (approved dose), objective response rates were 56.1% (central) and 71.2% (investigator) in laBCC and 7.7% (central) and 23.1% (investigator) in mBCC. Tumour responses were durable as follows: median duration of response was 26.1 months (central) and 15.7 months (investigator) in laBCC and 24.0 months (central) and 18.1 months (investigator) in mBCC. Five patients with laBCC and three with mBCC in the 200-mg arm died. Median overall survival was not reached in either population; 2-year overall survival rates were 93.2% (laBCC) and 69.3% (mBCC). In laBCC, efficacy was similar regardless of aggressive or non-aggressive histology. Sonidegib 200 mg continued to have a better safety profile than 800 mg, with lower rates of grade 3/4 adverse events (43.0% vs. 64.0%) and adverse events leading to discontinuation (30.4% vs. 40.0%). Conclusion Sonidegib continued to demonstrate long-term efficacy and safety in these populations. These data support the use of sonidegib 200 mg per local treatment guidelines.
Databáze: OpenAIRE