TY - JOUR
T1 - Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma
T2 - 30-month analysis of the randomized phase 2 BOLT study
AU - Lear, J. T.
AU - Migden, M. R.
AU - Lewis, K. D.
AU - Chang, A. L.S.
AU - Guminski, A.
AU - Gutzmer, R.
AU - Dirix, L.
AU - Combemale, P.
AU - Stratigos, A.
AU - Plummer, R.
AU - Castro, H.
AU - Yi, T.
AU - Mone, M.
AU - Zhou, J.
AU - Trefzer, U.
AU - Kaatz, M.
AU - Loquai, C.
AU - Kudchadkar, R.
AU - Sellami, D.
AU - Dummer, R.
N1 - Publisher Copyright:
© 2017 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.
PY - 2018/3
Y1 - 2018/3
N2 - 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–naïve 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.
AB - 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–naïve 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.
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U2 - 10.1111/jdv.14542
DO - 10.1111/jdv.14542
M3 - Article
C2 - 28846163
AN - SCOPUS:85032900146
SN - 0926-9959
VL - 32
SP - 372
EP - 381
JO - Journal of the European Academy of Dermatology and Venereology
JF - Journal of the European Academy of Dermatology and Venereology
IS - 3
ER -