Resolution of venous thrombo-emboli (VTE) with a factor Xa inhibitor: Initial safety and efficacy results of a randomized, phase III trial of anticoagulation plus inferior vena cava (IVC) filter versus anticoagulation alone in patients with cancer and VTE

Abstract

20544 Background: Cancer-associated thrombosis is a major cause of death in patients (pts) with cancer. The 1-year survival in pts with cancer with VTE is 12% (vs. 36% without VTE). More than 20% of pts have VTE propagation and re-thrombosis on standard therapeutic anticoagulation (AC) (Prandoni 2007). The role of IVC filters in terms of efficacy, safety, prevention of pulmonary embolism (PE), and impact on survival remains controversial. Resolution of DVT takes an average of 6 months in non-cancer pts (Asbeutah 2004) and thrombi remain detectable in half of pts after a year (Kearon 2004). Methods: Pts with malignancy were eligible if they had an acute VTE (DVT and/or PE), and were randomized to standard fondaparinux sodium (FS) alone [5mg SC for pts <50 kg, 7.5mg SC for pts 50–100 kg and 10mg SC for pts >100 kg] vs FS+IVC filter. A total of 106 pts are planned. The primary endpoint is survival without recurrent VTE. Secondary endpoints include safety and clot resolution, given in this report. Due to safety review in pts ≥ 65 yrs, the dose of FS was reduced to 5mg during the conduct of the study. Pts were evaluated q 2 weeks for 4 weeks then q 4 weeks. Results: To date 33 pts were randomized and treated. All have stage IV extent, 94% are on chemotherapy; median age 67 (range 38–89%). Diagnoses include: lung (25%), GI (22%), and breast (19%); 9% have brain metastases. Of pts re-evaluated with DVTs: 15/20, 75% [95% CI: 44–90%] had complete clot resolution at an average of 45 days. Of those with PE: 8/9, 89% [95% CI: 52–100%] had complete clot resolution. Toxicities were more prominent in pts ≥ 65, 1 with marked ecchymosis and 1 with fatal hemorrhage into a brain metastasis. Conclusions: This study is ongoing and remains blinded as to treatment arm; however, current observations are important: 1) complete clot resolution has been observed in many, despite past studies using low molecular weight heparins not reporting such resolution in cancer patients; 2) the factor Xa inhibition may be responsible for this clot resolution effect; 3) the FS was well tolerated and appears safe in those over age 65 at a lower dose. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline