The ultra-low molecular weight heparin (ULMWH) semuloparin for prevention of venous thromboembolism (VTE) in patients with cancer receiving chemotherapy: SAVE ONCO study

BACKGROUND:

Patients receiving chemotherapy for cancer are at increased risk for VTE; large randomized controlled trials (RCT) are needed to demonstrate benefit of antithrombotic prophylaxis. Semuloparin is a novel ULMWH with high anti-factor Xa and residual anti-factor IIa activities. We performed a multinational RCT to assess the efficacy and safety of semuloparin for VTE prevention in cancer patients receiving chemotherapy (SAVE-ONCO).

METHODS:

This was a double-blind study in patients with metastatic or locally advanced cancer of lung, colon-rectum, stomach, ovary, pancreas, or bladder, initiating a new chemotherapy course. Patients were randomized to receive subcutaneous semuloparin, 20 mg od, or placebo, until change of chemotherapy. The primary efficacy outcome was the composite of any symptomatic deep vein thrombosis (DVT), non fatal pulmonary embolism (PE) and VTE-related death. Clinically relevant bleeding was the main safety outcome. Outcomes were adjudicated by an independent Committee.

RESULTS:

Of 3,212 randomized patients, 68% had metastatic cancer; the majority had lung (37%) or colon-rectum (29%) cancer. Median treatment duration was ~3.5 months. Twenty of the 1,608 patients treated with semuloparin (1.2%) and 55 of the 1,604 patients treated with placebo (3.4%) had a thromboembolic event, representing a 64% risk reduction in such event rate (hazard ratio [HR]=0.36, 95% confidence interval [CI] 0.21–0.60, p<0.0001, intent-to-treat analysis). Treatment effect was consistent for DVT and PE, with a 59% risk reduction in PE rate (odds ratio 0.41, 95%CI 0.19–0.85). No heterogeneity in the benefit was observed for cancer type or stage. Nineteen of 1,589 patients (1.2%) in the semuloparin and 18 of the 1,583 patients (1.1%) in the placebo group had a major bleeding (HR=1.05, 95%CI 0.55 to 1.99). The rate of clinically relevant bleeding was 2.8% with semuloparin vs 2.0% with placebo (HR=1.40, 95%CI 0.89–2.21).

CONCLUSIONS:

We have demonstrated the benefit of thromboprophylaxis with semuloparin in patients receiving chemotherapy without increase in major bleeding. Such patients should be considered for thromboprophylaxis.