Gemcitabine and Platinum-Based Agents for the Prediction of Cancer-Associated Venous Thromboembolism: Results from the Vienna Cancer and Thrombosis Study

Gemcitabine and platinum-based agents could increase the risk of venous thromboembolism (VTE) in patients with cancer. We evaluated the additive predictive utility of these agents towards cancer-associated VTE beyond a recently developed and externally validated clinical prediction model, which was based on tumor entity and continuous D-dimer levels. Analysis was performed in the derivation cohort of this model, obtained from the Vienna Cancer and Thrombosis Study (CATS), a prospective observational cohort study (n = 1409). Patients were followed for the occurrence of VTE for a maximum of two years. Competing-risk analysis was performed to obtain cumulative incidences and to conduct between-group comparisons of VTE risk. Cumulative two-year incidences of VTE were not elevated with gemcitabine treatment (10.2% vs. 7.5%, p = 0.148), whereas they were higher for platinum-based therapy (11.6% vs. 5.9%, p < 0.001). In a multivariable analysis, adjusting for tumor site category and D-dimer, gemcitabine was not associated with increased risk of VTE (subdistribution hazard ratio (SHR) 0.82, 95% confidence interval (CI) 0.53-1.28, p = 0.390), whereas platinum-based therapy predicted for a numerically increased VTE risk (SHR 1.44, 95% CI 0.96-2.17, p = 0.080). Similar results were obtained in a sensitivity analysis (updated cohort, n = 1870). Our findings suggest limited additional value of chemotherapy for the prediction of cancer-associated VTE, beyond a validated clinical prediction model.