In an Australian phase III trial (TARGET-TP) reported in JAMA Oncology, Alexander et al found that ambulatory thromboprophylaxis reduced the risk of thromboembolic events in patients starting systemic therapy for lung or gastrointestinal cancer who were at elevated risk of thrombosis.
Study Details
The multicenter trial included 328 patients initiating systemic anticancer therapy for gastrointestinal cancer (n = 201) or lung cancer (n = 127) beginning in June 2018; a total of 132 patients had metastatic disease. Thromboembolism risk scores were based on fibrinogen and D-dimer levels; patients were stratified into low-risk (n = 128) and high-risk (n = 200) cohorts. Patients in the high-risk cohort were randomly assigned to receive enoxaparin at 40 mg subcutaneously daily (n = 100) for 90 days (up to 180 days according to ongoing risk) or no thromboprophylaxis (control; n = 100). The primary outcome was objectively confirmed thromboembolism at 180 days.
Key Findings
In the high-risk cohort, thromboembolism occurred in 8 patients (8%) in the enoxaparin group vs 23 patients (23%) in the control group (hazard ratio [HR] = 0.31, 95% confidence interval [CI] = 0.15–0.70, P = .005). The number needed to treat to prevent a thromboembolic event was 6.7.
In the low-risk cohort, thromboembolism occurred in 10 patients (8%). Risk of thromboembolism was significantly greater in the high-risk control group vs the low-risk group (HR = 3.33, 95% CI = 1.58–6.99, P = .002).
Major bleeding occurred in one patient (1%) in the enoxaparin group, two patients (2%) in the high-risk control group, and three patients (2%) in the low-risk group (overall P = .88). Mortality at 6 months was 13% in the enoxaparin group vs 26% in the high-risk control group (HR = 0.48, 95% CI = 0.24–0.93, P = .03). Mortality in the high-risk control group was significantly greater than in the low-risk group (7%; HR = 4.71, 95% CI = 2.13–10.42, P < .001).
The investigators concluded: “In this randomized clinical trial of individuals with lung and gastrointestinal cancers who were stratified by risk score according to thrombosis risk, risk-directed thromboprophylaxis reduced thromboembolism with a desirable number needed to treat, without safety concerns, and with reduced mortality. Individuals at low risk avoided unnecessary intervention. The findings suggest that biomarker-driven, risk-directed primary thromboprophylaxis is an appropriate approach in this population.”
Marliese Alexander, PhD, of the Pharmacy Department, Peter MacCallum Cancer Centre, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was supported by the Peter MacCallum Cancer Foundation, Victorian Cancer Agency, and Australian National Health and Medical Research Council. For full disclosures of the study authors, visit jamanetwork.com.
