(X) Structured Benefit-Risk for Enoxaparin Based on Real World Evidence Data in The Context of Its Label Extension for Treatment of Deep Vein Thrombosis and Pulmonary Embolism and Prevention of Its Recurrence in Active Cancer Patients

Publication Number: 314

Background: Venous thromboembolism (VTE) is a complication in cancer patients. VTE annual incidence is 1 of 200 in a population of cancer patients. Low molecular-weight heparins (LMWHs), including enoxaparin, have been recommended by international guidelines as the preferred treatment over direct oral anticoagulants (DOACs) and vitamin K antagonists (VKA) for the secondary prevention of cancer associated thrombosis (CAT). In Europe, until September 2021, only dalteparin and tinzaparin had this specific indication for cancer patients mentioned in their label.

Objectives: A structured benefit risk assessment (sBRA) was undertaken to compare the benefit risk (BR) profile of enoxaparin with other EU indicated LMWHs for the indication of extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of its recurrence in patients with active cancer.

Methods: The following steps of the sBRA framework were applied: decision context, determination of key benefit and risk outcomes, identification of data sources and adequate data extraction.
The only study to compare enoxaparin to other LMWHs was the observational study RIETECAT based on RIETE international registry of VTE patients.
The data presentation is based on value tree and forest plot - representing the adjusted hazard ratios with 95% confidence intervals for benefits and risks of enoxaparin versus other EU indicated LMWHs.

Results: The most clinically important benefits are the reduction in VTE recurrence and the reduction in all-cause mortality. “Major bleedings and minor bleedings events” are the most clinically important risks for this analysis. Regarding benefits, the comparison of enoxaparin with other EU indicated LMWHs showed a trend with favorable effects for enoxaparin for the reduction of VTE recurrence and the reduction in all-cause mortality, but no statistically significant difference was observed between the two groups. Regarding risks, the effect for major bleedings tended to be in favor of other LMWHs. For non-major bleeding, results tended to show a favorable effect for enoxaparin. However, there was no statistically significant difference between the two groups.

Conclusions: The sBRA facilitates the identification of critical issues and improves transparency of the assumptions used to evaluate the BR profile of a product.
Overall, the BR profile for enoxaparin is favorable and similar to that of other EU indicated LMWHs (dalteparin and tinzaparin) in the treatment of DVT and PE and prevention of its recurrence in patients with active cancer.