What’s The Best Treatment for VTE in Cancer?

Cancer can boost the risk of venous thromboembolism, or blood clots, due to hospitalization, chemotherapy, surgery, and the cancer itself. Practice guidelines recommend that cancer patients receive treatment with low-molecular-weight heparin (LMWH), but in recent years, the FDA has approved 4 direct oral anticoagulants (DOACs [dabigatran, rivaroxaban, apixaban, and edoxaban]) for treatment of VTE. However, the trials either excluded patients with cancer or included few people with cancer.

How do DOACs compare with LMWH for preventing recurrent VTE in patients with cancer? Deborah Schrag, MD, MPH, and colleagues from the Cancer Related VTE Anticoagulation Strategies (CANVAS) trial decided to find out.

In contrast to clinical trials that have compared specific DOACs with specific LMWHs in people with cancer, this study used a “pragmatic design”: Patients and physicians selected treatment either from among DOACs or from among LMWH or fondaparinux. The researchers also chose a noninferiority design because DOACs are more convenient compared with subcutaneously administered LMWH.

Their study included 638 patients with any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia who also had a new clinical or radiological diagnosis of VTE. In the DOAC and LMWH groups, respectively, 34% vs 32% had a highly thrombogenic tumor type (e.g., lung cancer, pancreatic cancer, gastroesophageal cancer, or ovarian cancer); 70% vs 68% had advanced cancer; 58% vs 56% had a pulmonary embolism; and 38% vs 44% had VTE first detected by imaging.

The participants were randomly assigned to either a DOAC (primarily apixaban and rivaroxaban) or LMWH (or fondaparinux) and were followed for 6 months or until death. Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. The primary outcome was the recurrent VTE rate at 6 months. Six secondary outcomes included major bleeding.

The researchers concluded that DOAC was non-inferior to LMWH — 6.1% in the DOAC group and 8.8% in the LMWH group developed recurrent VTE. Among participants with highly thrombogenic tumors, the cumulative incidence of recurrent VTE at 6 months was 9.0% for patients in the DOAC group and 12.2% in the LMWH group. (The researchers note that lower adherence rates with LMWH could have biased results toward noninferiority of DOAC therapy.)

Consistent with prior clinical trials, this trial found that patients treated with DOACs have a higher risk of clinically relevant nonmajor bleeding compared with patients treated with LMWH. However, none of the secondary outcomes were statistically significant; 5.2% of the DOAC group and 5.6% of the LMWH group had major bleeding.

Ten patients in the DOAC group and 3 in the LMWH group developed anemia of grade 3 or higher.At 6 months, 21.5% of patients in the DOAC group and 18.4% in the LMWH group had died.

There were no clinically meaningful differences in patient-reported health-related quality of life or perceived benefits and burdens of taking anticoagulant medication. The DOAC group, though, were significantly more likely to stick with their treatment, compared with the LMWH group. At 6 months, 70.9% of the DOAC patients and 59.4% of the LMWH patients were still taking their assigned anticoagulant. Of those assigned to LMWH, 6% (20/338) transitioned to warfarin therapy.