Abstract
Background
Patients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC), 2 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). Tumor 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. Tumor responses were durable: 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 3 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 nonaggressive 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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