Antithrombotic Prophylaxis Shown to Provide Clinical Benefit

Antithrombotic prophylaxis with ultra-low molecular weight heparin (ULMWH) may benefit patients treated with chemotherapy based on the findings of the SAVE-ONCO study. Daniel George, MD, of Duke University Medical Center, presented these data at the Patient and Survivor Care Oral Abstract Session held on Monday, June 6 (Abstract LBA9014).

The SAVE-ONCO study was a prospective, randomized, double-blind, multicenter, multicountry study in more than 3,200 patients with metastatic cancers. Patients received 20 mg of subcutaneous semuloparin once daily (1,608 patients) or placebo (1,604 patients) on the first day of chemotherapy until change of chemotherapy.

Semuloparin is a new agent in the class of ULMWH with a longer half-life compared with previous agents, such as enoxaparin. An injection given once daily is, therefore, sufficient for 24-hour coverage.

The primary efficacy outcome was time to first occurrence of any symptomatic deep vein thrombosis (DVT) or any pulmonary embolism (PE), either nonfatal PE or venous thromboembolism (VTE)-related death. Any clinically relevant bleeding was the main safety outcome of the study. The study was designed to show a risk reduction of VTE event rate of approximately 50% in patients taking semuloparin.

Of the 3,212 patients randomly assigned in the study, patients receiving prophylactic treatment with semuloparin were at 64% reduced risk for a thromboembolic event (hazard ratio: 0.36; 95% CI [0.21, 0.60]; p < 0.0001). Twenty of 1,608 (1.2%) patients treated with semuloparin and 55 of 1,604 patients (3.4%) treated with placebo had a thromboembolic event.

Treatment effect was similar for DVT and PE. For example, there was a 59% reduced risk in PE rate for patients receiving semuloparin (odds ratio: 0.41; 95% CI [0.19, 0.85]). Bleeding events were similar across both arms of the study. Clinically relevant bleeding rates of 2.8% and 2.0% were reported for patients receiving semuloparin or placebo, respectively.

Although risk for thromboembolism is high for patients with pancreatic, lung, and gastrointestinal cancers, the advantages of semuloparin were shown across a wide range of cancers. Based on current guidelines, thromboprophylaxis is recommended for patients undergoing surgery and for hospitalized and acutely ill patients.

Dr. George concluded that new data from this large SAVE-ONCO study show that prophylactic treatment is clinically useful for patients initiating chemotherapy for cancer. Vered Stearns, MD, of The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, discussed these data in reference to other studies such as PROTECHT, RE-COVER, and CONKO 004.

She indicated that predictive models are required that will provide guidance on ambulatory patients with cancer at the highest risk for VTE who may benefit from prophylaxis in the context of clinical outcomes.

"The SAVE-ONCO study is not likely to change clinical practice for ambulatory patients with cancer," Dr. Stearns concluded. "Ongoing subgroup analyses and evaluation of predictive markers may help select a population that will benefit from primary prophylaxis of VTE."