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 |
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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 |
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