Rivaroxaban thromboprophylaxis in ambulatory patients with pancreatic cancer: Results from a pre‐specified subgroup analysis of the randomized CASSINI study

Abstract

Background

Pancreatic cancer patients are at risk for venous thromboembolism (VTE); the value of thromboprophylaxis has not been definitively established.

Methods

This trial randomized cancer patients initiating a new regimen and at high risk for VTE (Khorana score ≥2) to rivaroxaban 10 mg or placebo up to day 180. This analysis examined the subset of pancreatic cancer patients. The primary efficacy endpoint was the composite of symptomatic deep‐vein thrombosis (DVT), asymptomatic proximal DVT, any pulmonary embolism, and VTE‐related death. The primary safety endpoint was International Society on Thrombosis and Haemostasis–defined major bleeding.

Results

In total, 49/1080 (4.5%) patients enrolled had baseline VTE on screening, with higher rates (24/362 [6.6%]) in pancreatic cancer and they were not randomized. Of 841 randomized patients, 273 (32.5%) had pancreatic cancer; 155/273 (57% in each arm) completed the double‐blind period. The primary endpoint occurred in 13/135 (9.6%) patients in the rivaroxaban group and in 18/138 (13.0%) in the placebo group (hazard ratio [HR] = 0.70; 95% CI, 0.34‐1.43; P = .328) in up‐to‐day‐180 period and 5/135 (3.7%) patients receiving rivaroxaban and 14/138 (10.1%) receiving placebo in the intervention period (HR = 0.35; 95% CI, 0.13‐0.97; P = .034). Major bleeding was similar (2 [1.5%] receiving rivaroxaban and 3 [2.3%] receiving placebo). Correlative biomarker studies demonstrated significant decline in D‐dimer (weeks 8 and 16) in patients randomized to rivaroxaban compared to placebo ( P < .01).

Conclusions

In ambulatory pancreatic cancer patients, rivaroxaban did not result in significantly lower incidence of VTE or VTE‐related death in the 180‐day period. During the intervention period, however, rivaroxaban substantially reduced VTE without increasing major bleeding, suggesting benefit of rivaroxaban prophylaxis in this setting.

Trial registration: ClinicalTrials.gov identifier, NCT02555878.

Abstract

Thromboprophylaxis with rivaroxaban is safe and effective in the prevention of venous thromboembolism in ambulatory patients with pancreatic cancer receiving systemic therapy, with a low number needed to treat. Given the favorable risk‐benefit ratio and convenience of the oral route of administration, these findings should inform guideline recommendations for high‐risk patients.