Direct oral anticoagulants significantly reduced risk for recurrence of cancer-associated venous thromboembolism compared with dalteparin among patients with cancer, according to study results published in Mayo Clinic Proceedings.
The findings suggest direct oral anticoagulants (DOACs) should be considered the standard-of-care treatment for adults with cancer-associated VTE, researchers noted.
“The landmark CLOT trial established low-molecular-weight heparin as the preferred anticoagulant therapy for cancer-associated VTE. However, low-molecular-weight heparin therapy has disadvantages, such as injection-site discomfort, ecchymosis and hematomas. It can negatively impact quality of life, which leads to poor compliance,” Irbaz Bin Riaz, MD, MS, researcher at Mayo Clinic in Rochester, Minnesota, told Healio. “DOACs have been compared against low-molecular-weight heparin for treatment of cancer-associated VTE in multiple clinical trials. We published a meta-analysis in 2019 that summarized the data for treatment of cancer-associated VTE at that time. These analyses are undertaken as a cross-sectional effort usually because there is little incentive for investigators to update the evidence, which is a laborious process, when new evidence becomes available.”
The 2020 Caravaggio trial prompted the current study because it provided additional data for apixaban (Eliquis; Bristol Myers Squibb, Pfizer), Riaz added.
“Contemporary guidelines were released before mature data on apixaban were published and, thus, endorsed the use of rivaroxaban [Xarelto, Janssen] and edoxaban [Savaysa, Daiichi Sankyo] but not apixaban for treatment of cancer-associated thrombosis,” he said. “The current updated analysis includes apixaban data and was meant to inform the forthcoming guidelines for treatment of cancer-associated VTE.”
Riaz and colleagues used a living, interactive evidence synthesis framework to assess the safety and efficacy of various DOACs among 2,894 patients with cancer-associated VTE included in four randomized controlled trials.
Results showed use of DOACs significantly decreased recurrent VTE events compared with dalteparin (Fragmin, Pfizer; OR = 0.59; 95% CI, 0.41-0.86) while not significantly increasing major bleeding events (OR = 1.34; 95% CI, 0.83-2.18).
Mixed treatment comparisons revealed apixaban (OR = 0.41; 95% CI, 0.16-0.95) and rivaroxaban (OR = 0.58; 95% CI, 0.37-0.9) significantly decreased recurrence of VTE events compared with dalteparin. However, edoxaban significantly increased major bleeding compared with dalteparin (OR = 1.73; 95% CI, 1.04-3.16) and rivaroxaban significantly increased clinically relevant nonmajor bleeding compared with dalteparin and other DOACs.
Of note, researchers observed no differences between DOACs regarding VTE recurrence and major bleeds.
“All DOACs — apixaban, rivaroxaban, edoxaban — had better efficacy when compared with dalteparin, but only apixaban appeared to have fewer bleeding events,” Riaz said. “Given the small number of trials in the study and associated uncertainties it is tough to pick the clear winner among DOACs.”
DOACs have been considered the standard of care to treat VTE in patients without cancer, and this analysis indicates the same is true for patients with cancer, according to the researchers.
“The choice of treatment for patients at high risk for bleeding, such as those with luminal tumors in the gastrointestinal or genitourinary tract, are more nuanced and need to be carefully individualized to the baseline risk of the patient sitting in front of you,” Riaz said. “Overall, clinicians can now be fairly comfortable with using DOACs in clinical practice to treat most patients with cancer-associated VTE. Among all DOACs, apixaban shows the most favorable bleeding profile, but we cannot be certain that it is clearly the best choice given the sparsity of data and nature of indirect comparisons. The choice of optimal DOAC is likely to be driven by local prescribing patterns, costs and access to a particular DOAC agent.”
Riaz and colleagues plan to update this analysis as soon as new data become available.
“We host all of this data on a living, interactive website, which means that clinicians and patients can look at our website and interact with these results and visualize the evidence for different treatments to see how they compare with each other,” Riaz said.
Irbaz Bin Riaz, MD, MS, can be reached at riaz.dr@mayo.edu.
Get the latest news and education delivered to your inbox
© 2022 Healio All Rights Reserved.
Get the latest news and education delivered to your inbox
© 2022 Healio All Rights Reserved.