Association between warfarin and survival in invasive melanoma: a population-based cohort study

Background Warfarin has been shown to reduce cancer risk via Vitamin K related AXL tyrosine kinase inhibition. Although AXL has been implicated in disease progression and therapy resistance in preclinical melanoma models, there are no clinical studies evaluating the impact of warfarin on melanoma prognosis. Hence, we sought to evaluate the relationship between warfarin and survival in melanoma. Methods We conducted a retrospective population-based cohort study of melanoma patients aged ≥ 65 years diagnosed between 2009–2013 from the Surveillance, Epidemiology, and End Results-Medicare database. Patients were grouped according to warfarin therapy 6 months prior and after melanoma diagnosis. Univariable and multivariable Cox proportional hazards models were used to compare overall (OS) and melanoma-specific survival (MSS) between groups. Results Overall, 10,778 patients with invasive melanoma were included. 13.2 % were prescribed warfarin, with atrial fibrillation being the most common indication (74.1 %). Warfarin prescription was associated with older age, male sex, and a greater number of comorbidities (all p < 0.001). Patients prescribed warfarin more frequently presented with ulceration, T3 and T4 disease, and stage II disease (all p < 0.05). Warfarin prescription was associated with greater MSS and OS in multivariable models (MSS adjusted hazard ratio [aHR] 0.72, 95 % CI 0.54–0.96, p = 0.02; OS aHR 0.88, 95 % CI 0.79–0.99, p = 0.04). Conclusions Warfarin was associated with greater MSS and OS among melanoma patients. These findings highlight the potential for Vitamin K related pathways to impact cancer specific activity. Further study of AXL and Vitamin K inhibition will be of significant interest in melanoma, targeted strategies actively under investigation.