Apixaban versus Dalteparin for the Treatment of Acute Venous Thromboembolism in Patients with Cancer: The Caravaggio Study

Abstract

International and national guidelines recommend low-molecular-weight heparin for the treatment of venous thromboembolism (VTE) in patients with cancer. The aim of the Caravaggio study is to assess whether oral apixaban is non-inferior to subcutaneous dalteparin for the treatment of acute proximal deep vein thrombosis and/or pulmonary embolism in patients with cancer. The study is an investigator-initiated, multi-national, prospective, randomized, open-label with blind end-point evaluation (PROBE), non-inferiority clinical trial (NCT03045406). Consecutive patients are randomized to receive oral apixaban or subcutaneous dalteparin for 6 months. Apixaban is given at a dose of 10 mg twice daily for the first 7 days and then 5 mg twice daily; dalteparin is given at a dose of 200 IU/kg for the first month and then 150 IU/kg once daily. The primary outcome of the study is objectively confirmed recurrent VTE as assessed by a central independent adjudication committee unaware of study treatment allocation. The primary safety outcome is major bleeding defined according to the guidelines of the International Society of Thrombosis and Haemostasis. Assuming a 6-month incidence of the primary outcome of 7% with dalteparin and an upper limit of the two-sided 95% confidence interval of the hazard ratio below the pre-specified margin of 2.00, 1,168 patients will be randomized considering an up to 20% loss in total patient-years ( = 80%; one-sided = 0.025). The Caravaggio study has the potential, along with other recently performed or on-going studies, to make less cumbersome the management of VTE in patients with cancer by replacing parenteral with oral anticoagulation.

SEOM clinical guideline of venous thromboembolism (VTE) and cancer (2019)

“…The mortality rate at 6 months was similar comparing apixaban with dalteparin (15.9 vs. 10.6%, HR 1.36, 95% CI 0.79-2.35). These results must be taken with caution and must await the final publication and the outcomes of Caravaggio trial [61] (NCT03045406), that will randomize 1168 patients to the same regimens of apixaban and dalteparin used in ADAM trial for 6 months. The primary outcome of the study is objectively confirmed recurrent VTE and this trial will be the largest trial ever performed in CAT treatment setting.…”

Interaction between chemotherapeutics and anticoagulants

“…Ciononostante, nella pratica clinica oncologica è ancora diffuso l'impiego di eparina a basso peso molecolare, raccomandata dalle linee guida per la profilassi del tromboembolismo venoso nei pazienti oncologici, ma per la quale non sono disponibili in letteratura evidenze a supporto dell'efficacia nei pazienti con FA. Lo studio CARAVAGGIO, attualmente in corso, confronterà direttamente apixaban e dalteparina nel trattamento della trombosi venosa acuta prossimale e/o dell'embolia polmonare in soggetti oncologici, allo scopo di convalidare la terapia anticoagulante orale rispetto a quella parenterale in questa tipologia di pazienti [4]. Al momento in alcuni Centri vige la tendenza a utilizzare enoxaparina nella fase acuta della FA (in Pronto Soccorso), per poi valutare il pas-saggio a un diverso farmaco anticoagulante per la terapia cronica; in altri invece viene valutato da subito l'eventuale impiego di NOAC.…”

Cancer‐associated venous thromboembolism: Treatment and prevention with rivaroxaban

“…The incidence of recurrent VTE was 0.7% with apixaban and 6.3% with dalteparin (HR, 0.099; 95% CI, 0.013‐0.780; P = .0281) . The CARAVAGGIO (apixaban for the treatment of venous thromboembolism in patients with cancer) trial, an investigator‐led, multinational, prospective, randomized trial that is currently ongoing, should provide further insight into the role of apixaban in the treatment of CAT . Table 6 summarizes the key characteristics and data from Hokusai‐VTE‐Cancer, SELECT‐D, and ADAM VTE studies.…”

“…Further studies regarding extended‐duration CAT treatment would be beneficial but will likely continue to be challenging to obtain. The upcoming DOAC studies for the treatment of CAT—CARAVAGGIO and CONKO‐011 (Rivaroxaban in the Treatment of VTE in Cancer Patients)—are assessing durations of therapy of ≤ 6 months …”