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

<h2>Abstract</h2><h3>Background</h3> Sonidegib display class-specific adverse events (AEs), which impair therapeutic adherence. Every-other-day administration is within the label of sonidegib approval. <h3>Objective</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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) and 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. <h3>Conclusion</h3> Switch to the every-other-day sonidegib schedule is safe and effective, albeit with reduced tumor control in the long-term.