Speakers and attendees during Poster Session 1 at the American Society of Hematology 61th Annual Meeting at the Orange County Convention Center, Friday December 6, 2019. Photo Courtesy American Society of Hematology © 2019 ASH/Nick Agro
Speakers and attendees during Poster Session 1 at the American Society of Hematology 61th Annual Meeting at the Orange County Convention Center, Friday December 6, 2019. Photo Courtesy American Society of Hematology © 2019 ASH/Nick Agro

Results from retrospective real-world data (RWD)* analyses reporting outcomes on the safety and effectiveness of apixaban (Eliquis®; Bristol-Myers Squibb and Pfizer), an oral selective Factor Xa inhibitor, compared to low molecular weight heparin (LMWH) or warfarin for the treatment of venous thromboembolism (VTE) in patients with cancer, were highlighted during the 2019 annual meeting of the American Society of Hematology (ASH), held December 7 – 10, 2019 in Orlando, Florida.

Deep vein thrombosis (DVT) is a condition in which a blood clot forms most often in the deep veins of the leg, groin or arm. Combined with pulmonary embolism (PE), in which blood cloths travel to the lungs where they cause blockages, these two conditions are known as venous thromboembolism (VTE) – a dangerous, potentially lethal medical condition.

VTE is the third most common cause of vascular death after heart attack and stroke. The disease can be a major health problem among patients with cancer.

A variety of studies have demonstrated that patients with cancer are at a significantly increased risk for VTE compared to those without cancer. VTE is also a leading cause of death in cancer patients, and a significant predictor for all-cause mortality.

Lower rates of major bleeding
The primary analysis of the data presented at ASH demonstrated that that apixaban 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. [1]

Apixaban 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.

The outcomes of the study were defined based on diagnosis codes and setting of care. [1]

Sub-group analyses
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. [2]

The findings of this study were generally consistent with the primary analysis.**

Alexander Cohen, MD, Consultant Physician, Department of Hematology at Guy’s and St. Thomas’ NHS Foundation Trust. Photo courtesy: NHS Foundation Trust.

Acropolis
The analyses of the two studies are part of ACROPOLIS™ (Apixaban ExperienCe Through Real-WOrld POpuLatIon Studies), a global real-world data analysis program developed by Bristol-Myers Squibb and Pfizer, designed to generate additional evidence from routine clinical practice settings to further inform healthcare decision makers, including healthcare providers and payers.

“Real-world evidence analyses such as this have the potential to provide additional insights into complex patient populations such as those with VTE and active cancer,” said Alexander Cohen, MD, Consultant Physician, Department of Hematology at Guy’s and St. Thomas’ NHS Foundation Trust.

“Results from these analyses are a welcomed addition to the growing body of data around recurrent VTE in patients with active cancer,” Cohen added.

However, while providing a robust source of complimentary information,  ACROPOLIS program provides a robust source of complementary information to healthcare professionals, the source and type of real-world data may limit how results and endpoints can be applied to the overall patient population. Hence, real-world data should not to be used as stand-alone evidence for healthcare decision making.

Real-world analyses
In these real-world analyses, four U.S. commercial insurance claims databases were used to identify VTE patients with 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.

Closely linked to cancer
“Cancer and VTE are closely linked. Patients with cancer have shown to be at increased risk of developing a blood clot,” said Roland Chen, MD, 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.

Limitations
However, 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.

“There is a growing opportunity to use real-world evidence to help inform the medical community, especially within complex patient populations, including those with active cancer and VTE,” noted Rory O’Connor, MD, Chief Medical Officer, Pfizer Internal Medicine.

“Data from real-world settings helps provide a more robust understanding of these patients and adds to the extensive body of real-world evidence evaluating the safety and effectiveness of apixaban.”


* Real-world evidence, also known as RWE, includes medical evidence obtained from real-world, observational, data obtained outside the context of randomized controlled trials and generated during routine clinical practice. The 21st Century Cures Act, which passed in 2016, places additional focus on the use of these types of data to support regulatory decision making, including approval of new indications for approved drugs.

** Anticoagulants, including apixaban, increase the risk of bleeding and can cause serious, potentially fatal bleeding. Please see important safety information for apixaban, including BOXED WARNING highlights of prescribing information.

References
[1] Cohen AT, Keshishian A, Lee T, Wygant G, Rosenblatt L, Hlavacek P, Mardekian J, et al. Safety and Effectiveness of Apixaban, LMWH, and Warfarin Among Venous Thromboembolism Patients with Active Cancer: A Retrospective Analysis Using Four US Claims Databases. 61st annual meeting of the American Society of Hematology (ASH). Program: Oral and Poster Abstracts (#326). Session: 901. [Abstract]
[2] Cohen AT, Keshishian A, Lee T, Wygant G, Rosenblatt L, Hlavacek P, Mardekian J, Wiederkehr D, Sah J, Luo X. Safety and Effectiveness of Apixaban, LMWH and Warfarin Among Venous Thromboembolism (VTE) Patients with Active Cancer: A Subgroup Analysis of VTE Risk Scale. 61st annual meeting of the American Society of Hematology (ASH). Program: Oral and Poster Abstracts (#327). Session: 901. [Abstract]

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