Switch to every-other-day sonidegib dose reduction schedule in advanced basal cell carcinoma: a multicenter retrospective observational study on effectiveness and safety

Background: Sonidegib displays class-specific adverse events (AEs), which impair therapeutic adherence. Every-other-day administration is within the label of sonidegib approval. Objective: to investigate the effectiveness and safety profile of every-other-day sonidegib in locally advanced basal cell carcinoma (laBCC) patients after a course of once-daily sonidegib. Methods: a multicenter retrospective observational study was performed at 15 Italian tertiary-referral centers (January 2016 – May 2024). Fisher's exact and Mann-Whitney test detected differences between the cohorts. Kaplan-Meier method estimated progression free survival (PFS). Univariate and multivariate logistic regressions investigated the association with switching to the every-other-day schedule. Results: 165 laBCC patients were enrolled, of whom 60 switched from once-daily to every-other-day sonidegib. Median sonidegib treatment duration was 14 months (range: 1–26) in the continuous regimen cohort, and 23 months (range: 6–29) in the reduced regimen cohort, p value < 0.0001. The objective response rate (ORR) was 80.8 % (95 % confidence interval [CI]: 87.4–72) and 84.8 % (95 % CI: 91.6–74.3) for patients on the once-daily and on the every-other-day sonidegib schedule, respectively. Median duration of response was 9.5 months (range: 1–37) and 6 months (range: 1–28) in the continuous and in the reduced regimen cohorts, respectively. PFS probability was reduced in the every-other-day sonidegib group compared to the once-daily group (hazard ratio: 4.8, 95 % CI: 1.10–21.27; p = 0.003). 62.6 % and 19.7 % patients experienced at least one AE on the once-daily and on the every-other-day schedule, respectively, p value < 0.0001. Conclusion: Switch to the every-other-day sonidegib schedule is safe and effective, albeit with reduced tumor control in the long-term.