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

Cancer Med. 2020 Sep;9(17):6196-6204. doi: 10.1002/cam4.3269. Epub 2020 Jul 14.

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.

Keywords: major bleeding; pancreatic cancer; rivaroxaban; thromboprophylaxis; venous thromboembolism.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Double-Blind Method
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Hemorrhage / chemically induced
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Outpatients*
  • Pancreatic Neoplasms / complications*
  • Placebos / therapeutic use
  • Pulmonary Embolism / etiology
  • Pulmonary Embolism / prevention & control*
  • Rivaroxaban / administration & dosage
  • Rivaroxaban / adverse effects
  • Rivaroxaban / therapeutic use*
  • Venous Thromboembolism / epidemiology
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / mortality
  • Venous Thromboembolism / prevention & control*

Substances

  • Anticoagulants
  • Fibrin Fibrinogen Degradation Products
  • Placebos
  • fibrin fragment D
  • Rivaroxaban

Associated data

  • ClinicalTrials.gov/NCT02555878