At-Home Blood Thinner Use During Systemic Therapy May Decrease Risk for Clots

Treatment with Xarelto (rivaroxaban) may reduce the risk for developing blood clots during active treatment with a systemic therapy like chemotherapy, according to results from the CASSINI trial.

In addition, results — which were presented at the 2018 American Society of Hematology (ASH) Annual Meeting – showed that treatment with the direct oral anticoagulant did not substantially increase risk for bleeding problems in patients.

Blood clots, such as venous thromboembolism (VTE), deep vein thrombosis (DVT) and pulmonary embolisms, are a common complication associated with cancer and its treatments. In turn, these complications can result in mortality, increased hospitalization, morbidity, treatment delays or a need for even more resource utilization, said Alok A. Khorana, M.D., professor of medicine at the Cleveland Clinic Lerner College of Medicine.

While blood thinners are typically administered in the hospital setting to reduce the risk for clots, there is a need for these agents to be prescribed more frequently for patients to take at home in order to reduce such a risk.

“In 2018, most of our cancer treatments take place in the outpatient setting, and so most (blood) clots occur in the outpatient setting. That’s really important because almost all of our efforts focused on preventing blood clots (is happening) in the inpatient setting,” Khorana said during a press conference at the meeting, held Dec. 1-4, in San Diego.

Previous studies showed there was a benefit to patients with cancer taking blood thinners at home (a self-administered injection of heparin), but doctors are not often forthcoming to prescribe this regimen that can be costly and hard to manage.

Therefore, Khorana and colleagues conducted the multinational, multicenter, randomized, double-blind, placebo-controlled superiority study — designed to evaluate the efficacy and safety of Xarelto compared with placebo for the treatment of thromboprophylaxis in ambulatory patients with cancer. The researchers aimed to assess the use of the oral blood thinner, while also restricting its use to patients at high risk for clots using a new systemic regimen Khorana and colleagues created to determine VTE risk, as indicated by a score of 2 or higher based on cancer type, blood test results and body mass index.

“About 10 years ago my research colleagues and I developed a score that helps predict patients who are risk for getting a blood clot, and that is helpful because if we target prevention toward high-risk patients, then the benefit would be greater and so the clinical benefit to patients would be greater,” Khorana said. “So, that was really our hypothesis going in to this clinical trial.”

The trial enrolled 1,080 adult patients starting a new systemic cancer treatment, of which 841 went on to randomization to receive either 10 mg of rivaroxaban once daily (420 patients) or placebo (421 patients) up to six months.

At six months, rates of clotting events — which included symptomatic or asymptomatic lower-extremity proximal DVT, symptomatic upper- or lower-extremity distal DVT and symptomatic or incidental pulmonary embolism and VTE-related death – were not significantly different between arms (6 percent with Xarelto vs 8.8 percent with placebo). However, Khorana explained this was due mainly to a large proportion of patients who stopped taking the drug before the end of the six-month period.

“The problem was that this is a cancer patient population getting chemotherapy, many of whom are switching chemotherapy drugs or progress on chemotherapy and switch to a different clinical drug,” he added. “So, about half of patients (in the entire study population) did not take the drug for the full six months.”

Therefore, the researchers were not surprised when the 38.7 percent of patients who discontinued treatment with the blood thinner during the six-month period went on to experience a clot event. “It’s not unexpected, because we know that if patients are not taking the drug, then you obviously won’t prevent a clot,” Khorana added.

When the researchers compared efficacy outcomes using a pre-specified analysis of all patients while they were actually on treatment with Xarelto, the blood thinner led to fewer clot events compared with placebo (2.6 percent vs. 6.4 percent, reducing the risk for a blood clot by 60 percent.

During both time periods, the researchers also evaluated the number needed to treat (NNT), or “how many patients have to take the drug to prevent a blood clot for one of them not to have a blood clot,” Khorana explained. In the six-month period, 35 patients would have had to have been treated to prevent one blood clot compared with 26 patients during the on-treatment period. “The clinical benefits continue to improve when you include secondary endpoints and the (on-treatment) endpoint,” he added.

At six months, a composite of clotting events and death from any cause was observed in just over 23 percent of patients on Xarelto and 29.5 percent of those on placebo.

Safety analyses were conducted for the on-treatment period only for patients who received at least one dose of the study drug (405 patients) or placebo (404 patients). Major bleeding occurred in eight patients in the Xarelto arm compared with four patients in the placebo arm, and clinically relevant non-major bleeding occurred in 11 and eight patients, respectively. The researchers noted side effects were comparable between groups.

Lastly, the risk score scale developed by the researchers identified patients who were at risk for VTE events both at baseline (4.5 percent) and during the study (8.8 percent), as well as 1.7 percent arterial events in the placebo group.

“Because nearly one-third of these events were at baseline, before patients have even started on chemotherapy, we wonder if baseline screening should be considered in patients start treatment with systemic therapy?” Khorana said. “Regardless, we believe our findings should inform future recommendations regarding thromboprophylaxis for higher-risk ambulatory cancer patients.”