Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase 2 randomised, double-blind BOLT study. The British journal of dermatology Dummer, R., Guminksi, A., Gutzmer, R., Lear, J. T., Lewis, K. D., Chang, A. L., Combemale, P., Dirix, L., Kaatz, M., Kudchadkar, R., Loquai, C., Plummer, R., Schulze, H., Stratigos, A. J., Trefzer, U., Squittieri, N., Migden, M. R. 2019


BACKGROUND: Basal cell carcinomas (BCCs) exhibit aberrant activation of the hedgehog pathway. Sonidegib is a hedgehog pathway inhibitor approved for the treatment of locally advanced BCC (laBCC) and metastatic BCC (mBCC) based on primary results of the BOLT (Basal Cell Carcinoma Outcomes with LDE225 [sonidegib] Treatment) study.PURPOSE: This is the final 42-month analysis of the BOLT study evaluating sonidegib efficacy and safety.METHODS: Adults with no prior hedgehog pathway inhibitor therapy were randomised in a 1:2 ratio to sonidegib 200 mg or 800 mg once daily. Treatment continued for up to 42 months or until disease progression, unacceptable toxicity, death, study termination, or withdrawal of consent. Primary efficacy endpoint was objective response rate (ORR) by central review, assessed at baseline, weeks 5, 9, and 17, then subsequently every 8 or 12 weeks during years 1 or 2, respectively. Safety endpoints included adverse event monitoring and reporting.RESULTS: The study enrolled 230 patients, 79 and 151 in the 200 mg and 800 mg groups, respectively, of whom 8% and 3% remained on treatment by the 42-month cutoff, respectively. The ORR by central review (95% confidence interval [CI]) was 56·1 (43·3-68·3)% for laBCC and 7·7 (0·2-36·0)% for mBCC in the 200 mg group and 46·1 (37·2-55·1)% for laBCC and 17·4 (5·0-38·8)% for mBCC in the 800 mg group. No new safety concerns emerged.CONCLUSIONS: Sonidegib demonstrated sustained efficacy and a manageable safety profile. Final BOLT results support sonidegib as a viable treatment option for laBCC and mBCC.

View details for DOI 10.1111/bjd.18552

View details for PubMedID 31545507