DOAC Works in Cancer-Related VTE, No Tradeoff in Bleeds

The direct oral anticoagulant (DOAC) apixaban (Eliquis) was as good as the low molecular weight heparin dalteparin (Fragmin) for the treatment of patients with cancer-associated thrombosis — with no increase in risk of major bleeding to boot, the CARAVAGGIO trial showed.

In cancer patients who had a newly diagnosed symptomatic or incidental proximal lower-limb deep vein thrombosis (DVT) or pulmonary embolism (PE), 6 months on one of these drugs led to similar rates of recurrent venous thromboembolism (VTE):

• Overall VTE: 5.6% with apixaban vs 7.9% with dalteparin (HR 0.63, 95% CI 0.37-1.07, P<0.001 for non-inferiority)
• Recurrent DVT: 2.3% vs 2.6% (HR 0.87, 95% CI 0.34-2.21)
• Recurrent PE: 3.3% vs 5.5% (HR 0.54, 95% CI 0.29-1.03)
• Fatal PE: 0.7% vs 0.5% (HR 1.93, 95% CI 0.40-9.41)

As for safety, major bleeding — including ISTH-criteria bleeds and those that required acute surgical intervention — was no more common with apixaban than dalteparin (3.8% vs 4.0%, HR 0.82, 95% CI 0.40-1.69), reported Giancarlo Agnelli, MD, of University of Perugia in Italy, during a late-breaking trial session at the virtual American College of Cardiology (ACC) meeting. The findings were published simultaneously online in the New England Journal of Medicine.

“Taken together, these findings may expand the proportion of patients with both cancer and VTE who would be eligible for treatment with apixaban, including patients with gastrointestinal cancer,” the investigators concluded.

Agnelli suggested that the indication for apixaban use could be expanded based on these data: “It’s certainly an advancement in terms of practicality.”

“I was particularly impressed by the low rate of bleeding, which has traditionally been a concern with DOACs,” said ACC session discussant Bonnie Ky, MD, of the Hospital of the University of Pennsylvania in Philadelphia.

Major guidelines currently recommend low-molecular weight heparin, edoxaban (Savaysa), and rivaroxaban (Xarelto) as VTE treatment options for patients with cancer.

The open-label CARAVAGGIO trial had 1,170 cancer patients randomized to the oral factor Xa inhibitor apixaban or the conventional therapy of subcutaneous dalteparin. Apixaban users were to take the DOAC 10 mg twice daily for the first 7 days, then 5 mg twice daily. The dalteparin group received it at a dose of 200 IU/kg once daily for the first month, then 150 IU/kg once daily.

Average age of patients was 67. About half were men, and 97% of participants had active cancer.

“Patients with a large variety of cancer types, including approximately one third that occurred at gastrointestinal sites, were included in the trial, which was consistent with the cancer distribution in the general population. Cancers associated with high thromboembolic risk, such as lung and colorectal cancers, were well represented,” the investigators noted.

For safety reasons, cancer patients were not eligible for enrollment if they had basal cell or squamous cell carcinoma of the skin, primary brain tumor, known cerebral metastases, or acute leukemia. Moreover, their cancer, whether active or not, had to have been diagnosed within 2 years of study enrollment.

Apixaban was more effective than dalteparin at preventing recurrent VTE in patients younger than age 65.

“The apparent decrease in efficacy with increasing age that was shown in the subgroup analysis should be considered as hypothesis generating and warrants attention in future studies,” the authors cautioned.

Other limitations of the trial include its open-label design and the lack of statistical power to make definitive conclusions about bleeding. Additionally, it is unclear what the effect is of apixaban taken for longer than 6 months among cancer patients with VTE.

Moreover, without a head-to-head comparison, the heterogeneity in the DOAC trials makes it “inappropriate to conclude that one DOAC is better than another,” according to Agnes Lee, MD, of University of British Columbia, Vancouver Coastal Health, and the British Columbia Cancer Agency.

“So how do we choose which anticoagulant to use? Carefully! Clinicians need to rely on a detailed clinical history, ascertaining the cancer type, status, and treatment, along with bleeding risk, concomitant medications, and the patient’s experiences and values,” Lee wrote in an accompanying editorial.

“Since the landscape of cancer therapy and survival is rapidly changing, anticoagulant therapy in patients with cancer needs to keep pace. DOACs mark a welcome step forward in providing effective and safe therapeutic choices for patients with cancer and VTE,” she concluded.