"Apixaban for Thromboprophylaxis in Cancer Patients". The New England Journal of Medicine. 2018. 378:711-719. PubMed • Full text • PDF

Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

In ambulatory patients with cancer at intermediate-to-high risk for venous thromboembolism who are starting chemotherapy, does thromboprophylaxis with apixaban reduce the incidence of venous thromboembolism compared with placebo?

Bottom Line

Apixaban significantly reduced the incidence of venous thromboembolism in ambulatory patients with cancer at intermediate-to-high risk who were starting chemotherapy, at the expense of an increased risk of major bleeding episodes.

Major Points

Guidelines

As of this trial's publication, guidelines for thromboprophylaxis in cancer patients were not established based on the findings of this study.

Design

Multicenter, randomized, placebo-controlled, double-blind trial
N=574 patients
Randomized 1:1 to receive apixaban or placebo
Treatment period: 180 days
Median follow-up: 183 days

Population

Inclusion Criteria
-Newly diagnosed cancer or progression after remission
-Initiating new chemotherapy course
-Khorana score ≥2
-Age ≥18 years

Exclusion Criteria
-Risk factors for significant bleeding
-Hepatic disease with coagulopathy
-Certain cancer diagnoses (basal-cell/squamous-cell skin cancer, acute leukemia, or myeloproliferative neoplasm)
-Planned stem-cell transplantation
-Life expectancy <6 months
-Renal insufficiency, platelet count <50,000 per cubic millimeter

Baseline Characteristics
-Mean age 61 years
-58.2% women
-Most common cancers: gynecologic (25.8%), lymphoma (25.3%), and pancreatic (13.6%)
-22.8% were using antiplatelet or NSAIDs

Interventions

-Apixaban: 2.5 mg twice daily
-Placebo: identical tablets twice daily

Outcomes

Primary Outcome
-Venous thromboembolism: 4.2% in apixaban group vs. 10.2% in placebo group (hazard ratio, 0.41; 95% CI, 0.26 to 0.65; P<0.001)

Secondary Outcomes
-Major bleeding: 3.5% in apixaban group vs. 1.8% in placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P=0.046)

Criticisms

-Limited ability to make definitive conclusions about individual tumor types or chemotherapy regimens based on sample size.
-Results may be less applicable to patients with significant renal dysfunction.

Funding

Supported by Canadian Institutes of Health Research and Bristol-Myers Squibb–Pfizer Alliance.

Further Reading

The full article can be accessed at NEJM.org.