Vitamin D insufficiency and risk of taxane-induced peripheral neuropathy: Results from SWOG S1714.

12012 Background: Taxane-induced peripheral neuropathy (TIPN) affects up to 70% of patients treated with taxanes and can lead to functional impairment, reduced quality of life, and treatment disruption. There are no proven TIPN preventive strategies. Vitamin D insufficiency is a modifiable factor that has been linked to increased TIPN risk in paclitaxel-treated patients with breast cancer. We analyzed the association between baseline vitamin D levels and TIPN among patients receiving taxane-based treatments in a large, multicenter, prospective cohort study (SWOG S1714). Methods: In a prespecified analysis, baseline vitamin D levels were quantified from plasma samples using liquid chromatography-tandem mass spectrometry. Vitamin D insufficiency was defined as total 25-hydroxyvitamin D ≤20 ng/mL. The primary endpoint was development of TIPN, defined as an increase of ³8 points from baseline in the sensory subscale of the EORTC QLQ-CIPN20 (0-100 scale, with higher score indicating worse symptoms) by week 24. The secondary endpoint was the greatest worsening from baseline in the sensory subscale CIPN20 score. Multivariable Cox proportional hazards model was used to evaluate time to initial development of TIPN and linear regression was used for the secondary endpoint, both adjusting for age, cancer stage, race/ethnicity, comorbidities, taxane type, and planned treatment duration. Statistical significance was set at α = 0.05. Results: Among 1278 evaluable patients, 610 had available serum samples for vitamin D analysis (mean age 54.8 years [standard deviation 11.9]; 98% female; 85% White; 90% breast cancer; 59% paclitaxel-treated). Of these, 134 (22%) were vitamin D insufficient at baseline, and 383 (63%) developed TIPN during 24 weeks of follow-up. At baseline, CIPN20 sensory score did not differ by vitamin D status (p = 0.70). Baseline vitamin D insufficiency was significantly associated with higher risk of TIPN (adjusted hazard ratio 1.35; 95% confidence interval [CI] 1.06-1.72; p = 0.013). Patients with vitamin D insufficiency had more severe worsening of neuropathy (greatest worsening in CIPN20 sensory score: mean 23.4 vs. 18.5 points; adjusted mean difference 4.7 points; 95% CI 1.0-8.4; p = 0.013). Conclusions: Baseline vitamin D insufficiency was associated with significantly increased risk and severity of TIPN in this prospective cohort of patients receiving taxane-based therapy across multiple cancer types. These findings highlight vitamin D status as a potentially modifiable biomarker for TIPN risk and support clinical trials of vitamin D supplementation as a TIPN prevention strategy.