Melina Verso1, Giancarlo Agnelli2, Andrés Munoz3, Jean M Connors4, Olivier Sanchez5, Menno Huisman6, Benjamin Brenner7, Gualberto Gussoni8, Alexander T Cohen9, Cecilia Becattini1. 1. Internal, Vascular and Emergency Medicine - Stroke Unit, University of Perugia, Perugia, Italy. 2. Internal, Vascular and Emergency Medicine - Stroke Unit, University of Perugia, Perugia, Italy. Electronic address: giancarlo.agnelli@unipg.it. 3. Medical Oncology Service, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain. 4. Brigham and Women's Hospital, Hematology Division, Harvard Medical School, Boston, United States. 5. Université de Paris, Service de Pneumologie et Soins Intensifs, AP-HP, Hôpital Européen Georges Pompidou, INSERM UMR-S 1140 Innovative Therapies in Haemostasis, F-75006, Paris, France; F-CRIN INNOVTE, F-42000, St-Etienne, France. 6. Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands. 7. Institute of Hematology and BMT Rambam Health Care Campus Technion, Israel Institute of Technology Haifa, Israel. 8. Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti (FADOI) Research Center, Milan, Italy. 9. Guy's and St. Thomas' NHS Foundation Trust Hospital, King's College London, London, United Kingdom.
Abstract
BACKGROUND: Patients with cancer-associated venous thromboembolism (VTE) have a high risk of VTE recurrence and anticoagulant treatment-related bleeding, but the correlation of these risks with the cancer stage is unclear. METHODS: We evaluated the risks of VTE recurrence and treatment-related major bleeding according to the cancer stage in patients with VTE and solid cancer randomised to apixaban or dalteparin in the Caravaggio study. Cancer stage was categorised by expert cancer physicians according to pre-specified criteria, and study outcomes were adjudicated by an independent committee unaware of cancer stage and treatment allocation. RESULTS: Of the 1034 patients included in this analysis, 217 (21.0%) had localised cancer, 279 (27.0%) locally advanced cancer and 503 (48.7%) metastatic cancer. Cancer stage was undetermined in 35 patients (3.4%). VTE recurrence and major bleeding rates were 2.8% and 3.2% in patients with localised cancer, respectively. In comparison to patients with localised cancer, the VTE recurrence rate was higher in patients with locally advanced cancer (7.5%, hazard ratio [HR] = 2.8, 95% confidence interval [CI] = 1.1-6.9) and metastatic cancer (8.7%, HR = 3.3, CI = 1.4-7.7, CI). Patients with metastatic cancer had numerically increased major bleedings compared to those with localised cancer (5.2%, HR = 1.65, CI = 0.7-3.8). The efficacy and safety of apixaban and dalteparin across patients with different cancer stages were consistent with the findings observed in the overall patients with cancer randomised in the study. CONCLUSIONS: Patients with locally advanced and metastatic cancer have a higher rate of VTE recurrence than patients with localised cancer with no statistically significant difference in treatment-related major bleeding.
BACKGROUND: Patients with cancer-associated venous thromboembolism (VTE) have a high risk of VTE recurrence and anticoagulant treatment-related bleeding, but the correlation of these risks with the cancer stage is unclear. METHODS: We evaluated the risks of VTE recurrence and treatment-related major bleeding according to the cancer stage in patients with VTE and solid cancer randomised to apixaban or dalteparin in the Caravaggio study. Cancer stage was categorised by expert cancer physicians according to pre-specified criteria, and study outcomes were adjudicated by an independent committee unaware of cancer stage and treatment allocation. RESULTS: Of the 1034 patients included in this analysis, 217 (21.0%) had localised cancer, 279 (27.0%) locally advanced cancer and 503 (48.7%) metastatic cancer. Cancer stage was undetermined in 35 patients (3.4%). VTE recurrence and major bleeding rates were 2.8% and 3.2% in patients with localised cancer, respectively. In comparison to patients with localised cancer, the VTE recurrence rate was higher in patients with locally advanced cancer (7.5%, hazard ratio [HR] = 2.8, 95% confidence interval [CI] = 1.1-6.9) and metastatic cancer (8.7%, HR = 3.3, CI = 1.4-7.7, CI). Patients with metastatic cancer had numerically increased major bleedings compared to those with localised cancer (5.2%, HR = 1.65, CI = 0.7-3.8). The efficacy and safety of apixaban and dalteparin across patients with different cancer stages were consistent with the findings observed in the overall patients with cancer randomised in the study. CONCLUSIONS: Patients with locally advanced and metastatic cancer have a higher rate of VTE recurrence than patients with localised cancer with no statistically significant difference in treatment-related major bleeding.