Real-World data analysis of Eliquis for the treatment of venous thromboembolism in patients with active cancer.- BMS + Pfizer

The Bristol-Myers Squibb-Pfizer Alliance announced results from retrospective real-world data analyses reporting outcomes on the safety and effectiveness of Eliquis (apixaban) compared to low molecular weight heparin (LMWH) or warfarin for the treatment of venous thromboembolism (VTE) in patients with active cancer (n=14,086).

The real-world data analyses were highlighted during oral presentations at the American Society of Hematology (ASH) Annual Meeting in Orlando, Florida. Results from the primary analysis showed that Eliquis use was associated with lower rates of major bleeding (MB) (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.47-0.86, p=0.003), clinically-relevant non-major (CRNM) bleeding (HR: 0.81, 95% CI: 0.70-0.94, p=0.006) and recurrent VTE (HR: 0.61, 95% CI: 0.47-0.81, p=0.001) compared to LMWH. Eliquis was also associated with a lower rate of recurrent VTE (HR: 0.68, 95% CI: 0.52-0.90, p=0.007) and similar rates of major bleeding (HR: 0.73, 95% CI: 0.53-1.0, p=0.051) and CRNM bleeding (HR: 0.89, 95% CI: 0.77-1.04, p=0.145) compared to warfarin. Outcomes were defined based on diagnosis codes and setting of care.

In a second oral presentation, results from a sub-group analysis of the primary study were highlighted based on different levels of risk for developing recurrent VTE, a blood clot most often found in the legs or lungs. Study findings were generally consistent with the primary analysis. It is important to note that, anticoagulants, including Eliquis, increase the risk of bleeding and can cause serious, potentially fatal bleeding.

In these real-world analyses, four U.S. commercial insurance claims databases were used to identify VTE patients with active cancer (defined as cancer diagnosis or cancer treatment [chemotherapy, radiation and/or cancer-related surgery] within six months before or 30 days after VTE diagnosis) who initiated apixaban, LMWH, or warfarin within 30 days following the first VTE event. The risk of events was evaluated using a Cox proportional hazard model. Inverse probability treatment weighting (IPTW) was used to balance patient characteristics between apixaban, LMWH, and warfarin cohorts. Patients were followed to the earliest of: health plan disenrollment, death, index therapy discontinuation, switch to another anticoagulant, study end, or a maximum of 6 months. This was done to evaluate the rates of MB, CRNMB, and recurrent VTE (fatal or non-fatal) among VTE patients with active cancer prescribed apixaban, LMWH, or warfarin in routine clinical practice.

�Cancer and VTE are closely linked. Patients with cancer have shown to be at increased risk of developing a blood clot,� said Roland Chen, M.D., Vice President, Head of Clinical Development, Innovative Medicines, Bristol-Myers Squibb. �Given this risk and the medical complexities in patients with active cancers, it is important to increase awareness of symptoms related to VTE and bolster the visibility of this patient population to help improve health outcomes.�

Real-world data have the potential to complement randomized, controlled clinical trial data by providing additional information about how a medicine performs in routine medical practice. Real-world data analyses also have several limitations. For example, the source and type of data used may limit the generalizability of the results and endpoints. Observational real-world studies can only evaluate association and not causality, and despite the use of methods to address measured confounding, residual confounding may still be present. Due to these limitations, real-world data analyses are not used as stand-alone evidence to validate the efficacy and/or safety of a treatment. Additionally, data regarding cancer stage, laboratory test results, biomarkers, and medications prescribed during hospitalization were not available. Mortality and fatal recurrent VTE could not be evaluated because commercial databases do not have complete death information.

Comment: VTE is the third most common cause of vascular death after heart attack and stroke. VTE can be a major health problem among patients with cancer, with studies showing that patients with cancer are at a significantly increased risk for VTE compared to those without cancer.ii VTE is also a leading cause of death in cancer patients, and a significant predictor for all-cause mortality.