Net clinical benefit of 18-month over 6-month rivaroxaban in patients with cancer and acute low-risk pulmonary embolism: Insight from the ONCO PE trial

Background/Introduction The ONCO PE trial showed the potential benefit of extended anticoagulation therapy with rivaroxaban in patients with cancer and acute low-risk pulmonary embolism (PE) of the simplified version of the Pulmonary Embolism Severity Index (sPESI) score of 1 with respect to recurrent venous thromboembolism (VTE) events. However, it also suggested a potential signal for an increased risk of bleeding with an 18-month compared to 6-month rivaroxaban treatment duration. Purpose This post-hoc analysis aimed to compare the net clinical benefit (NCB) of an 18-month compared to 6-month rivaroxaban treatment duration. Methods The ONCO PE trial was a multicenter, open-label, randomized controlled trial, in which patients with cancer and acute low-risk of the sPESI score of 1 were randomly assigned (1:1) to the 18-month or 6-month rivaroxaban treatment group. Firstly, we assessed the net adverse clinical events (NACE), which were defined as a simple combination of the thrombotic and bleeding events, in each treatment group. We defined NACE-1 as a composite endpoint of recurrent VTE or major bleeding at 18 months. In addition, to assess the broader spectrum of events, we defined NACE-2 as a composite endpoint of recurrent VTE or all clinically relevant bleeding at 18 months. Secondly, we assessed the NCB of 18-month compared to 6-month rivaroxaban, which was defined as the sum of the differences in the incidence of thrombotic and bleeding events between the 2 treatment groups. We set the bleeding weight as 1.0 in the base case analyses. The NCB-1 and NCB-2 corresponded to NACE-1 and NACE-2, respectively. We calculated the NCB with the bleeding weights set at 0.5 and 2. Results Of the 178 eligible patients, 89 were in the 18-month group and 89 in the 6-month group. With a bleeding weight of 1.0, the incidence rates of NACE-1 were 10.8 (95% CI, 6.0–19.5) events per 100 person-years in the 18-month group and 18.6 (95% CI, 11.9–29.2) in the 6-month group (incidence rate ratio [IRR], 0.61; 95% CI, 0.29–1.29). The NCB-1 was 9.0% (95% CI, -1.9% to 19.9%). The incidence rates of NACE-2 were 25.1 (95% CI, 16.7–37.7) events per 100 person-years in the 18-month group and 34.5 (95% CI, 24.3–49.1) in the 6-month group (IRR, 0.79; 95% CI, 0.46–1.35). The NCB-2 was 9.0% (95% CI, -4.5% to 22.4%). As the bleeding weights increased from 0.5 to 2, the NCB-1 became attenuated from 10.7% (95% CI, 0.7% to 20.7%) to 5.6% (95% CI, -6.7% to 18.0%) (Figure A), and the NCB-2 also became attenuated from 10.7% (95% CI, -1.0% to 22.3%) to 5.6% (95% CI, -9.0% to 20.3%) (Figure B). Conclusions The NCB of the 18-month compared to 6-month rivaroxaban treatment duration was not significant, although the 18-month treatment had a numerically lower incidence of NACE than the 6-month treatment.