Efficacy Following Discontinuation of Sonidegib Treatment in Patients With Locally Advanced Basal Cell Carcinoma: Results From the BOLT 42-Month Analysis

Introduction: Sonidegib, a Hedgehog (HH) pathway inhibitor, is approved for the treatment of locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiation. The pivotal 42-month BOLT (NCT01327053) study demonstrated sustained efficacy and manageable safety of sonidegib. Prior analyses at 18 months demonstrated clinical benefit persisting beyond sonidegib discontinuation. Pharmacokinetic modeling suggests HH pathway inhibition can be maintained following discontinuation. This analysis presents the efficacy of sonidegib 200 mg daily in patients with laBCC who discontinued treatment without disease progression (PD) at 42 months (end of study). Methods: BOLT was a randomized, double-blind, placebo-controlled, Phase 2 study. Objective response rates (ORRs; complete response + partial response), duration of response (DOR), and progression-free survival (PFS) were assessed by central and investigator review per modified response evaluation criteria in solid tumors (mRECIST). Adverse events (AEs) were also assessed. Results: Of the 66 patients with laBCC randomized to sonidegib 200 mg daily, 37 discontinued treatment without PD. The ORRs for these patients per central (57% [n = 20]) and investigator (73% [n = 27]) review were similar to the overall patient population (61% [n = 40] and 71% [n = 47] per central and investigator review, respectively). For patients who discontinued treatment, the median (95% confidence interval [CI]) DOR per central and investigator review was not estimable (NE) and 20.2 months (12.0, NE), respectively. The median PFS (95% CI) per central and investigator review was NE and 22.0 months (16.6, NE), respectively. Most AEs were Grades 1/2 in severity. Conclusion: In this 42-month analysis among patients with laBCC who received sonidegib 200 mg daily, clinical benefit was observed beyond treatment discontinuation during this study.