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ELIQUIS® (apixaban) is indicated for prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (NVAF), with one or more risk factors, such as prior stroke or transient ischaemic attack (TIA), age ≥75 years, hypertension, diabetes mellitus, symptomatic heart failure (NYHA Class ≥II); treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults; and, prevention of venous thromboembolic events (VTE) in patients who have undergone elective hip or knee replacement surgery.


CARAVAGGIO Clinical Trial

In the CARAVAGGIO clinical trial, ELIQUIS® demonstrated comparable efficacy to dalteparin for the treatment of VTE in patients with cancer, with no statistically significant increase in major bleeding.1

Patients with active cancer can be at high risk of both VTE and bleeding events. When ELIQUIS is considered for DVT or PE treatment in cancer patients, a careful assessment of the benefits against the risks should be made.2 ELIQUIS is contraindicated in patients with malignant neoplasms at high risk of bleeding.2

The CARAVAGGIO trial was powered to inform the primary efficacy* outcome. Hierarchical testing was not carried out for bleeding results and therefore these results should be interpreted with caution.1

CARAVAGGIO was supported by a research grant from the Bristol-Myers Squibb (BMS) / Pfizer Alliance. The Alliance did not have any role in trial design, conduct, collection or analysis of the data, or the review of editing of the manuscript.1

ELIQUIS is an oral treatment option for VTE in your patients with cancer that:2

has no bridging
requirements

can be taken with or
without food

The latest NICE guidelines recommend considering a DOAC in appropriate patients with confirmed proximal DVT / PE, and active cancer.3 Choice of anticoagulant should take into account tumour site, drug-drug interactions and bleeding risk.3

Watch the video below to learn more about the CARAVAGGIO trial.

Discover the data supporting ELIQUIS for the treatment of VTE in patients with cancer.

To assess whether ELIQUIS was non-inferior to dalteparin (LMWH) for the prevention of recurrent VTE in patients with cancer, without increasing the risk of major bleeding.1†

CARAVAGGIO was an independent investigator-initiated PROBE trial. Patients with cancer and newly diagnosed VTE were randomised in a 1:1 ratio to receive either ELIQUIS or dalteparin for 6 months1

Selected inclusion criteria:1,4,5

  • Newly diagnosed symptomatic or incidental proximal lower-limb DVT, symptomatic or incidental PE, or both
  • Active cancer (defined as cancer diagnosed within the past 6 months, cancer for which anticancer treatment was being given at the time of enrollment or during 6 months before randomisation, or recurrent locally advanced or metastatic cancer) or a history of cancer including those in whom a diagnosis had been made within 2 years before enrollment
  • Any confirmed cancer type other than basal cell or squamous cell carcinoma of the skin, primary brain tumour, known intracerebral metastases, or acute leukaemia

Selected exclusion criteria:1,4,5

  • ECOG Performance Status III or IV
  • Life expectancy <6 months
  • Active bleeding
  • Haemoglobin level <8 g/dl (5.0 mmol/l) or platelet count <75 x 109/l or history of heparin-induced thrombocytopaenia
  • CrCl <30 ml/min
  • Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg) despite antihypertensive treatment
  • Concomitant use of strong inhibitors or inducers of both CYP3A4 and P-gp
  • Concomitant thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor), or >165 mg aspirin per day, or dual antiplatelet therapy
  • Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase level 3 times or more and / or bilirubin level 2 times or more the upper limit of the normal range

For a full list of the inclusion / exclusion criteria, please see the CARAVAGGIO supplementary appendix.4

At 6 months

Primary outcome (powered for non-inferiority)

Recurrent VTE*

Primary safety outcome

Major bleeding§

Selected secondary safety outcome

CRNM bleeding

ELIQUIS demonstrated comparable efficacy to dalteparin for the treatment of VTE in patients with cancer, with no statistically significant increase in major bleeding1

The CARAVAGGIO trial was powered to inform the primary efficacy outcome. Hierarchical testing was not carried out for bleeding results and therefore these results should be interpreted with caution.1 Any confirmed cancer type other than basal cell or squamous cell carcinoma of the skin, primary brain tumour, known cerebral metastases, or acute leukaemia was eligible for inclusion in the trial.1

Rates of major GI and non-GI bleeding with ELIQUIS vs. dalteparin in patients with cancer were also assessed1

Limitations of the CARAVAGGIO clinical trial:1

  • It was an open-label trial to avoid the use of parenteral placebo for 6 months
  • GI bleeding was not a prespecified trial outcome
  • Patients with brain tumours, known cerebral metastases, or acute leukaemia were not enrolled for safety reasons, so the results cannot be extrapolated to those patient groups
  • The sample size was powered for the primary outcome (recurrent VTE) and was not powered to make definitive conclusions about bleeding

CARAVAGGIO provides data on the efficacy and safety of ELIQUIS for the treatment of VTE in patients with cancer1

FOOTNOTES

* The primary outcome was objectively confirmed recurrent VTE, which included proximal DVT of the lower limbs (symptomatic or incidental), symptomatic DVT of the upper limbs, and PE (symptomatic, incidental, or fatal) occurring during the 6-month trial period.1 Two of the VTE recurrences in the ELIQUIS group were upper-extremity DVT. The primary outcome of the trial was also the primary efficacy outcome.1

Once non-inferiority was met, superiority was tested for as a secondary analysis.1

Incidental DVT or PE were unsuspected events detected by imaging performed for reasons other than clinical suspicion of VTE. The maximum proportion of patients entering the study with incidental VTE was set at 20% of the overall study population, as only a limited proportion of these patients were included in randomised controlled trials on VTE treatment in cancer patients.5

§ The primary safety outcome was major bleeding, which was defined as acute clinically overt bleeding associated with one or more of the following: a decrease in the haemoglobin level of ≥2 g/dl, a transfusion of ≥2 units of red cells, bleeding occurring at a critical site (intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, or retroperitoneal), bleeding resulting in surgical intervention, or fatal bleeding, all occurring during the trial-period through 72 hours after the last dose was administered.1 One patient in the ELIQUIS group had an event that was categorised as major bleeding since it resulted in surgical intervention.1

CRNM bleeding was defined as acute clinically overt bleeding that does not meet the criteria for major and consists of: any bleeding compromising haemodynamics; spontaneous haematoma larger than 25cm3, or 100 cm2 if there was a traumatic cause; intramuscular haematoma documented by ultrasonography; epistaxis or gingival bleeding requiring tamponade or other medical intervention or bleeding from venipuncture for >5 minutes; haematuria that was macroscopic and was spontaneous or lasted for >24 hours after invasive procedures; haemoptysis, haematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention; or any other bleeding considered to have clinical consequences for a patient, such as medical intervention, the need for unscheduled contact (visit or telephone call) with a physician, or temporary cessation of a study drug, or associated with pain or impairment of activities of daily life.4

BD = Twice Daily   CI = Confidence Interval   CrCl = Creatinine Clearance   CRNM = Clinically Relevant Non-Major   CYP3A4 = Cytochrome P450 3A4   DOAC = Direct-acting Oral Anticoagulant   
DVT = Deep Vein Thrombosis   ECOG = Eastern Cooperative Oncology Group   
HR = Hazard Ratio   IU = International Units   
LMWH = Low Molecular Weight Heparin   OD = Once Daily   P-gp = P-glycoprotein   
PE = Pulmonary Embolism   PROBE = Prospective Randomised Open-label Blinded Endpoint   
SC = Subcutaneous   UFH = Unfractionated Heparin   VTE = Venous Thromboembolism

REFERENCES

  1. Agnelli et al. N Engl J Med 2020; 382; 1599–1607.
  2. ELIQUIS® (apixaban) Summary of Product Characteristics. Available at www.medicines.org.uk.
  3. NICE guideline [NG158]. Venous thromboembolic diseases: diagnosis, management, and thrombophilia testing. March 2020.
  4. Agnelli et al. N Engl J Med 2020; 382; 1599–1607. Supplementary appendix.
  5. Agnelli et al. Thromb Haemost 2018; 118; 1668–1678.