ASH 2018: CASSINI Trial: Rivaroxaban Thromboprophylaxis for VTE Prevention in Patients With Cancer
A new study suggests taking a direct oral anticoagulant (DOAC) can reduce the risk of harmful blood clots in patients undergoing cancer treatments, without substantially increasing the risk of bleeding problems. Findings from the CASSINI trial were presented by Khorana et al at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract LBA1).
Blood clots in veins and arteries are a common complication from cancer and its treatments, and thrombotic events such as pulmonary embolism, stroke, and heart attack are the second-leading cause of death among patients with cancer. Anticoagulants are commonly administered in the hospital setting to reduce the risk of these clots, but anticoagulants are not frequently prescribed for patients with cancer to take at home.
“Since almost all chemotherapy is done in the outpatient setting, giving prophylactic anticoagulants only when patients are in the hospital doesn’t prevent a majority of the clots, most of which occur in the outpatient setting,” said lead study author Alok A. Khorana, MD, of Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, in a statement.
CASSINI Methods
The new CASSINI study is the first to assess the use of DOACs, taken as a daily pill, and to restrict the regimen to patients at high risk for clots. It compared rates of thrombotic events in patients randomly assigned to take a placebo or the DOAC rivaroxaban (Xarelto).
The primary efficacy endpoint was a composite of objectively confirmed symptomatic or asymptomatic lower-extremity proximal deep-vein thrombosis (DVT), symptomatic upper- or lower-extremity distal DVT, symptomatic or incidental pulmonary embolism, and venous thromboembolism (VTE)-related death.
The trial enrolled 1,080 adult patients starting a new systemic cancer treatment, typically chemotherapy. All of the participants faced an increased risk of venous thromboembolism, as indicated by a score of 2 or higher on the Khorana risk scale, which is based on cancer type, blood test results, and body mass index. After screening, 841 patients were assigned to take rivaroxaban or placebo daily for up to 180 days.
Researchers tracked thrombotic events and participants underwent an ultrasound of the legs every eight weeks to detect clots that were not symptomatic. At 180 days, rates of clotting events were not statistically significantly different between the rivaroxaban group (just under 6%) and the placebo group (about 8.8%). However, the difference was more marked during the on-treatment period, during which 2.6% of patients taking rivaroxaban and 6.4% of patients taking placebo experienced a primary endpoint event.
Trial Findings
The primary efficacy endpoint occurred in 25 of 420 patients (5.95%) and 37 of 421 patients (8.79%) (hazard ratio [HR]= 0.66; 95% confidence interval [CI] = 0.40–1.09; P = .101) in the rivaroxaban and placebo groups (number needed to treat = 35), respectively, in the up-to-day 180 observation period.
The trial did not meet statistical significance for the primary analysis period of 180 days, mainly because a large proportion of patients stopped taking the drug (or placebo) earlier than 180 days. More than half of those assigned to placebo and nearly 44% of those assigned to take rivaroxaban stopped the regimen before 180 days, and more than one-third of clotting events occurred after participants had discontinued their assigned regimen. In a prespecified supportive analysis focused on the period in which participants were actually taking rivaroxaban or placebo, those taking rivaroxaban showed a substantially reduced risk of clotting—6.90% vs 10.70%, respectively (HR = 0.62; 95% CI = 0.39–0.99; P = .04).
“Despite the fact that the reduction in venous thromboembolism was not statistically significant during the primary analysis period, the drug was clearly effective in reducing the rates of venous thromboembolism on treatment,” said Dr. Khorana. “Taking rivaroxaban worked as long as the patients kept taking it.”
At 180 days, a composite of clotting events and death from any cause was observed in just over 23% of patients on rivaroxaban and 29.5% of those on placebo.
Anticoagulants increase the risk of bleeding. While bleeding was more common among those receiving rivaroxaban, rates of bleeding complications were on par with other studies of direct oral anticoagulants and lower than those commonly seen with heparin, according to Dr. Khorana. Just under 2% of those taking rivaroxaban and 1% of those taking placebo experienced major bleeding, while nonmajor bleeding occurred in 2.7% of those taking rivaroxaban and 2% of those taking placebo.
The researchers plan to analyze whether further stratifying patients by risk score or by cancer type could further clarify the benefits of taking DOACs.
The trial was co-sponsored by Bayer and Janssen.
Disclosure: See the study authors’ full disclosures at ash.confex.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
