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

SIMPLE SUMMARY: Certain chemotherapy agents (gemcitabine, platinum-based agents) have been suggested to increase the risk of venous thromboembolism in cancer patients. Our aim was to evaluate, whether treatment with these agents can be used to better predict the risk of cancer-associated venous thromboembolism. Within a prospective observational cohort study, including 1409 patients, we found that treatment with gemcitabine and/or platinum-based agents is only of limited value in predicting the risk of venous thromboembolism beyond known risk factors included in an established risk prediction model (tumor type, blood levels of D-dimer). These findings suggest that a large part of the observed rate of venous thromboembolism in patients treated with these agents might be related to the underlying thrombotic risk rather than the agent itself. ABSTRACT: 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.