The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma

J Am Acad Dermatol. 2016 Jul;75(1):113-125.e5. doi: 10.1016/j.jaad.2016.02.1226. Epub 2016 Apr 7.


Background: The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study.

Objective: This report provides long-term follow-up data collected up to 12 months after the last patient was randomized.

Methods: In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review.

Results: Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively).

Limitations: No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved.

Conclusion: With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC.

Keywords: Basal Cell Carcinoma Outcomes with LDE225 Treatment study; advanced basal cell carcinoma; hedgehog pathway inhibitor; locally advanced basal cell carcinoma; metastatic basal cell carcinoma; sonidegib.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biphenyl Compounds / administration & dosage
  • Biphenyl Compounds / adverse effects
  • Biphenyl Compounds / therapeutic use*
  • Carcinoma, Basal Cell / drug therapy*
  • Carcinoma, Basal Cell / secondary
  • Disease Progression
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Smoothened Receptor / antagonists & inhibitors
  • Survival Rate
  • Young Adult


  • Antineoplastic Agents
  • Biphenyl Compounds
  • Pyridines
  • Smoothened Receptor
  • sonidegib