Rivaroxaban thromboprohylaxis in ambulatory patients with pancreatic cancer: Results from a prespecified subgroup analysis of the CASSINI study

4016 Background: Rivaroxaban thromboprophylaxis has been shown to reduce venous thromboembolism (VTE) on-treatment in ambulatory cancer patients in a recent randomized trial. Pancreatic cancer patients are at substantial risk for VTE; value of thromboprophylaxis has not been definitively established. Methods: CASSINI was a double-blind placebo-controlled trial of cancer patients initiating a new regimen, at high risk for VTE (Khorana score ≥2), randomized to rivaroxaban 10 mg daily or placebo up to 180 days. Patients were stratified by presence or absence of pancreatic cancer. Patients had screening ultrasound and blood drawn at baseline and every 8 wks. Primary efficacy endpoint was a composite of symptomatic DVT, asymptomatic proximal DVT, any PE and VTE-related death. Primary safety endpoint was International Society on Thrombosis and Hemostasis (ISTH)-defined major bleeding. Results: Of 1080 patients enrolled, 49 (4.5%) failed screening due to baseline VTE, with even higher rates [24/362 (6.6%)] in patients with pancreatic cancer. Of 841 randomized patients, 273 (32.6%) had pancreatic cancer with median age 66 y; 57% male and 155/273 (57% in each arm) completing the double-blind period. During intervention (on-treatment) period, 5/135 (3.7%) pancreatic cancer patients in the rivaroxaban arm and 14/138 (10.1%) in placebo arm had primary endpoint events [HR 0.35; 95%CI (0.13, 0.97), p = 0.03; number needed to treat, NNT = 16]. Major bleeding was not increased, occurring in 2 (1.5%) patients in rivaroxaban arm and 3 (2.3%) in placebo arm. Further benefit with rivaroxaban was observed when including primary and secondary endpoints (arterial/visceral events): 6/135 (4%) events in rivaroxaban vs 17/138 (12%) in placebo [HR, 0.34; 95%CI (0.14, 0.87), P = 0.02; NNT = 13]. Correlative biomarker studies demonstrated significant decline in D-dimer values over time (weeks 8 and 16) in patients without VTE randomized to rivaroxaban prophylaxis compared to placebo (P < 0.01), supporting clinical findings. Conclusions: Rivaroxaban substantially reduced VTE in pancreatic cancer patients during intervention period. Given no increase in major bleeding, our findings suggest benefit to rivaroxaban thromboprophylaxis in pancreatic cancer patients initiating systemic therapy. Clinical trial information: NCT02555878.