Semuloparin Is Effective and Safe for Antithrombotic Prophylaxis in Cancer Patients

Giancarlo Agnelli, MD

The investigational ultra-low-molecular-weight heparin semuloparin significantly decreases the risk of thromboembolic events in cancer patients initiating chemotherapy compared with placebo, and without a hike in major bleeding, according to the results of the SAVE-ONCO trial.

“This study showed the clinical benefit of thromboprophylaxis with semuloparin in a large group of patients across a broad representation of cancers, both locally advanced and metastatic disease, and a wide range of chemotherapy regimens,” said Giancarlo Agnelli, MD, with University of Perugia, Italy, and associates.

Overall, 3212 patients were randomized to subcutaneous semuloparin 20 mg once daily or placebo for at least three months or until a change in their chemotherapy regimen. Semuloparin has high anti-factor-Xa and minimal anti-factor—IIa activities.

Venous thromboembolism (VTE) is a serious and potentially lethal complication for cancer patients receiving chemotherapy, and patients with malignancy have a significantly increased VTE risk compared with patients without malignancy, the authors observed. VTE risk in these patients also depended on the site and stage of the primary cancer, type and intensity of the chemotherapy regimen, age, comorbidities, and Eastern Cooperative Oncology Group (ECOG) performance status.

Present guidelines recommend antithrombotic prophylaxis for cancer patients who are hospitalized for medical illness, and for patients who have undergone surgery for cancer, the investigators added. Routine antithrombotic prophylaxis, however, is not recommended in ambulatory cancer patients receiving chemotherapy because of a lack of randomized clinical studies demonstrating a favorable benefit-to-risk ratio of anticoagulants in this setting.

Patients were eligible for enrollment in the present study if they had metastatic or locally advanced solid tumors and were initiating a new chemotherapy regimen for locally advanced or metastatic solid tumors.

The primary efficacy outcome was the composite of any symptomatic deep-vein thrombosis, any nonfatal pulmonary embolism (PE), and death related to VTE. The median treatment duration was 3.5 months in both treatment groups.

In an intent-to-treat analysis, treatment with semuloparin led to a 64% risk reduction in the incidence of the primary efficacy outcome versus placebo of 1.2% versus 3.4% (hazard ratio (HR) = 0.36; 95% CI, 0.21-0.60; P < .0001).

“

This study showed the clinical benefit of thromboprophylaxis with semuloparin in a large group of patients across a broad representation of cancers, both locally advanced and metastatic disease, and a wide range of chemotherapy regimens.”

—Giancarlo Agnelli, MD

Semuloparin was associated with a reduction in the risk of both DVT (odds ratio [OR], 0.32; 95% CI, 0.15-0.62) and fatal and nonfatal PE (OR, 0.41; 95% CI, 0.19-0.85).

The treatment effect on the primary endpoint was consistent in subgroups defined by the primary site and stage of cancer and the baseline risk of VTE.

The incidence of clinically relevant bleeding was 2.8% with semuloparin and 2.0% with placebo (HR = 1.40; CI, 0.89-2.21) with a similar incidence of major bleeding: 1.2 versus 1.1% (HR = 1.05; CI, 0.55-1.99).

The authors said that while their study showed that semuloparin-based thromboprophylaxis benefits a broad population of cancer patients, stratification for the risk of VTE might be useful.

Agnelli G, George DJ, Kakkar AK, et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med. 2012;366:601-609.