DOACs are noninferior to low-molecular-weight heparins for preventing recurrent cancer-associated VTE, results from a ‘pragmatic’ study of routine oncology practice show.

The findings add to the body of evidence for the efficacy and safety of DOACs obtained from single-drug trials, according to US researchers, who said DOACS offer the convenience of oral dosing over ‘burdensome’ subcutaneous administration of LMWH.

Published in JAMA [link here], the CANVAS study comprised 638 adults with haematological cancers or solid tumours and either a symptomatic or asymptomatic VTE detected on imaging studies within 30 days of enrolment.

The study found patients randomised to a DOAC, most commonly apixaban and rivaroxaban, had a recurrent VTE rate of 6.1% at six months compared to 8.8% in patients randomised to LMWH – meeting the criteria for non-inferiority.

About a third of the cohort had highly thrombogenic tumours such as pancreas, lung, oesophagus and ovarian cancer.

A subgroup analysis, found the cumulative incidence of recurrent VTE at six months in these patients was 9.0% in the DOAC group and 12.2% in the LMWH group

In secondary outcomes for the whole cohort, major bleeding occurred in 5.2% of the DOAC group and 5.6% of the LMWH group and minor bleeding occurred in 8.0% of the DOAC group and 11.4% of the LMWH group.

However the study authors noted that, consistent with prior clinical trials, patients treated with DOACs had a higher risk of clinically significant non-major bleeding compared with patients treated with LMWH [5.8% v 2.6%]. They postulated that the lack of difference in major bleeding events may have been because apixapan accounted for 59% of DOAC use in the trial, and this drug was associated with lower rates of bleeding than other DOACs.

Death at six months occurred in 21.5% of patients in the DOAC group and 18.4% in the LMWH group.

There were no clinically meaningful differences between the groups in patient-reported health-related quality of life or in the patients’ perceived benefits and burdens of their anticoagulant treatment.

However adherence to the assigned anticoagulation therapy at six months was significantly greater for the DOAC group compared with the LMWH group (70.9% v 58.4%), which may partly reflect the more convenient oral route of administration with DOACs compared with subcutaneously administered LMWH.

While this trial found non-inferiority for #DOAC as compared to LMWH with respect to recurrent #VTE, it just barely missed the non-inferiority margin for major bleeding (despite a point estimate favoring DOACs). So I feel re-assured in prescribing DOACs for #Cancer-VTE

— Geoff Barnes (@GBarnesMD) June 4, 2023

The investigators said their findings were consistent with a number of single-drug clinical trials of DOACs and cancer-related VTE including the CARAVAGGIO and ADAM-VTE (apixaban v dalteparin) and SELECT-D (rivaroxaban v dalteparin) studies.

“In contrast to previous randomised clinical trials of DOAC therapy for patients with cancer and VTE, this study was pragmatic and represented routine oncology practice by allowing clinicians and patients to select a drug from within a class and modify doses or stop therapy for procedures,”

“Because patients with advanced cancer and brain metastases, impaired performance status, and reduced liver or kidney function were enrolled, results are likely to be more generalisable to patients encountered in oncology practice.”

“These findings support use of a DOAC to prevent recurrent VTE in patients with cancer,” they concluded.