Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase II randomized, double-blind BOLT study

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 study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment]. Objectives This is the final 42-month analysis of the BOLT study, evaluating the efficacy and safety of sonidegib. Methods Adults with no prior hedgehog pathway inhibitor therapy were randomized 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. The primary efficacy end point was the 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 end points 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 3.3% remained on treatment by the 42-month cutoff, respectively. The ORRs by central review were 56% [95% confidence interval (CI) 43-68] for laBCC and 8% (95% CI 0 center dot 2-36) for mBCC in the 200-mg group and 46 center dot 1% (95% CI 37 center dot 2-55 center dot 1) for laBCC and 17% (95% CI 5-39) for mBCC in the 800-mg group. No new safety concerns emerged. Conclusions Sonidegib demonstrated sustained efficacy and a manageable safety profile. The final BOLT results support sonidegib as a viable treatment option for laBCC and mBCC.