Rivaroxaban effective as thromboprophylaxis during anticancer treatment
SAN DIEGO — Rivaroxaban prophylaxis significantly reduced thromboembolic events among patients receiving systemic cancer therapy, according to findings of a double-blind, randomized, placebo-controlled study presented at the late-breaking abstract session of ASH Annual Meeting and Exposition.
“It has been known for 100 years, if not longer, that patients with cancer often suffer from blood clots, typically venous clots,” Alok A. Khorana, MD, Sondra and Stephen Hardis chair in oncology research and vice chair for clinical services of Taussig Cancer Institute and director of the gastrointestinal malignancies program at Cleveland Clinic, told HemOnc Today. “Most clots occur in the outpatient setting. From a public health perspective, that’s really important, because almost all of our efforts at preventing blood clots have taken place in an inpatient setting.”
Khorana suggested that a risk-adapted approach using the Khorana scoring system, along with 10 mg rivaroxaban (Xarelto, Janssen) once daily, may improve on previous attempts at thromboprophylaxis in populations of patients with cancer.
A way of measuring efficacy of thromboprophylaxis is to determine the number of patients needed to treat in order to prevent one event, he added.
“Around 50 patients would need to take an injection every day for one of them not to get a blood clot,” he said, noting that these findings were reported in previous studies.
In the parallel-group, multicenter study, Khorana and colleagues evaluated the safety and efficacy of rivaroxaban compared with placebo among 841 ambulatory patients with cancer who were initiating new systemic cancer therapy and were deemed high risk for venous thromboembolism, defined as a Khorana score of 2 or greater.
In total, 274 (32.6%) had pancreatic cancer, 698 (83%) were white and 428 (50.9%) were men.
Researchers randomly assigned patients 1:1 to 10 mg once daily rivaroxaban or placebo up to day 180.
A composite of objectively confirmed symptomatic or asymptomatic lower-extremity proximal deep vein thrombosis, symptomatic upper- or lower-extremity distal DVT, symptomatic or incidental pulmonary embolism, and VTE-related death served as the primary efficacy endpoint.
The primary efficacy endpoint occurred in 5.95% of patients on active treatment and 8.79% of those in the placebo group (HR = 0.66; 95% CI, 0.4-1.09).
However, Khorana noted that 37.8% of those events occurred in patients who had discontinued the drug.
“It was a challenge to keep patients on the study for 6 months,” Khorana told HemOnc Today. “Many of them went off the study at a certain time point. On average, patients stayed on the study drug for 4.5 months, but we still kept them in the active therapy group. We used a very conservative methodology so our data would be robust.”
Thus, when the group looked at events for patients while on treatment, the thromboembolic event rates were 2.62% for rivaroxaban and 6.41% for placebo (HR = 0.4; 95% CI, 0.2-0.8).
Rates of the secondary endpoint — which was a composite of the primary endpoint and all-cause mortality through 180 days — were 23.1% in the active therapy group and 29.5% for placebo (HR = 0.75; 95% CI, 0.57-0.97).
Results of an analysis of the number of patients needed to treat to prevent an event showed that, using the primary endpoint, it would require treating 26 patients to prevent one event. When the primary efficacy endpoint plus arterial and visceral VTE were included while on treatment, that number dropped to 20 patients.
Moreover, the number of patients who would undergo treatment before experiencing an event was 101 for major bleeding and 135 for nonmajor bleeding.
“This number needed to treat is a model we use for public health issues in a large population of patients,” Khorana said. “If you’re in the 20 to 30 range, you’re doing well; this has good public health significance. In our study, if you count all events, that number is 17.”
Safety outcomes showed that major bleeding occurred in 1.98% of patients in the rivaroxaban group and 0.99% of those in the placebo group (HR = 1.96; 95% CI, 0.59-6.49). Clinically nonrelevant major bleeding rates also were slightly higher in the rivaroxaban group, at 2.72% vs. 1.98% (HR = 1.34; 95% CI, 0.54-3.32).
“There were no abnormal safety signals,” Khorana said. “Major bleeding rates were quite low.
“These findings should inform future recommendations regarding thromboprophylaxis
for higher-risk ambulatory cancer patients,” he added. – by Rob Volansky
Khorana A, et al. Abstract LBA-1. Presented at: ASH Annual Meeting and Exposition; Dec. 1-4, 2018; San Diego.
Disclosures : Khorana reports relationships with AngioDynamics, Bayer, Halozyme, Janssen, LeoPharma, Medscape/WebMD, Parexel, Pfizer, Pharmacyclics, PharmaCyte, Sanofi, Seattle Genetics and TriSalus. Please see the abstract for all other authors’ relevant financial disclosures.