The role of pretreatment vitamin D insufficiency in racial disparity in taxane-induced peripheral neuropathy: Results from the SWOG S0221 trial.

12136 Background: Taxane-induced peripheral neuropathy (TIPN) affects up to 70% of patients receiving taxanes and can lead to severe, irreversible symptoms that impair daily functioning and quality of life. Approximately 25% of patients require taxane dose modification or discontinuation to prevent TIPN, compromising treatment effectiveness and survival. Self-reported Black patients experience nearly two times greater incidence of TIPN compared to White patients, contributing to treatment alterations and worse cancer outcomes. Vitamin D insufficiency, which is more common among Black patients, has been implicated as a modifiable risk factor for TIPN. This study assessed the extent to which vitamin D insufficiency mediates the racial disparity in TIPN. Methods: This secondary analysis included self-reported Black or White female patients with early-stage breast cancer treated with paclitaxel-based chemotherapy on the SWOG S0221 phase III trial. The primary endpoint was clinician-assessed grade ≥3 sensory neuropathy per NCI CTCAE attributed to paclitaxel. The mediator was pretreatment vitamin D insufficiency, defined as total 25-hydroxyvitamin D ≤20 ng/mL. Causal mediation analysis decomposed the total effect of race on TIPN into its direct effect and an indirect effect mediated through vitamin D insufficiency, adjusted for age and paclitaxel regimen (weekly or every other week). Log-linear model with modified Poisson regression and weighted logistic regression were used for the outcome model and the mediator model, respectively. Confidence intervals were computed via bootstrapping, and significance was set at α=0.05. Results: A total of 1,106 participants (mean age 51.2 SD 10 years) were included, of whom 109 were Black and 997 were White. Black patients had a higher prevalence of vitamin D insufficiency (77% vs. 28%, p <0.001) and a higher incidence of grade ≥3 sensory TIPN (29% vs. 14%, p <0.001). The adjusted risk ratio (RR) for TIPN comparing Black to White patients was 2.24 (95% CI, 1.54-3.19; p <0.001). Vitamin D insufficiency statistically mediated this association, with an indirect effect RR of 1.18 (95% CI, 1.01-1.38; p = 0.048), accounting for 27% of the racial disparity in TIPN. The direct effect of race on TIPN, independent of vitamin D status, remained significant (RR 1.90; 95% CI, 1.30-2.85; p <0.001). Conclusions: Vitamin D insufficiency contributes to, but does not entirely explain, the racial disparity in TIPN. While other unaccounted factors may interact with or modify this association, vitamin D supplementation in insufficient patients could partially reduce racial disparities in TIPN and improve pharmacoequity.