Thromboprophylaxis Reduces Thromboembolism/Mortality in Lung and GI Cancer

High-risk patients were randomly assigned 1:1 to receive 40 mg of enoxaparin subcutaneously daily for up to 90 or 180 days according to ongoing risk or no thromboprophylaxis.

Treatment with risk-directed thromboprophylaxis reduced thromboembolism and mortality without safety concerns in patients with gastrointestinal (GI) and lung cancers, according to findings from the phase 3 Targeted Thromboprophylaxis in Ambulatory Patients Receiving Anticancer Therapies (TARGET-TP) trial (ACTRN12618000811202).

Investigators reported thromboembolism in 8% of patients randomly assigned to receive enoxaparin compared with 23% of those assigned to receive no thromboprophylaxis (HR, 0.31; 95% CI, 0.15-0.70; P = .005; number needed to treat [NNT], 6.7). Additionally, 8% of low-risk patients assigned to observation experienced thromboembolism (high-risk control vs low-risk; HR, 3.33; 95% CI, 1.58-6.99; P = .002).

A post hoc intervention period analysis indicated that 2% and 23% of patients assigned to enoxaparin and control treatment, respectively, had thromboembolism (HR, 0.10; 95% CI, 0.02-0.44; P = .02; NNT, 4.8). Additionally, thromboembolism affected 28% of the TARGET-TP lung cancer control population and 19% of those with GI cancer. The rate of thromboembolism in the low-risk population was 5% when excluding catheter-related and arterial events.

Treatment with enoxaparin correlated with significant reductions in 6-month all-cause mortality (13%) compared with the control (26%; HR, 0.48; 95% CI, 0.24-0.93; P = .03). The rates of cancer progression in each respective group were 42% vs 47% (HR, 0.78; 95% CI, 0.51-1.19; P = .25). Additionally, the 6-month all-cause mortality rate in low-risk patients was 7% (high-risk control vs low risk; HR, 4.71; 95% CI, 2.13-10.42; P <.001), and the cancer progression rate at the same period was 27% (high-risk control vs low risk; HR, 2.14; 95% CI, 1.38-3.12; P = .001).

“The fibrinogen and D-dimer risk assessment model [RAM] identified individuals with lung and [GI] cancers who would most benefit from thromboprophylaxis and those who could avoid intervention,” the study authors wrote. “Future investigations in expanded tumor groups that incorporate clinician and consumer preference for choice of anticoagulant are warranted.”

Investigators of the open-label randomized TARGET-TP trial assessed adult patients receiving systemic anti-cancer treatment for lung or GI cancers in Australia. Patients were stratified into low-risk or high-risk cohorts based on fibrinogen and D-dimer levels. High-risk patients were randomly assigned 1:1 to receive 40 mg of enoxaparin subcutaneously daily for up to 90 or 180 days according to ongoing risk or no thromboprophylaxis.

The trial’s primary end point was the rate of thromboembolism at 180 days. Secondary end points included major bleeding, survival, and evaluating the sensitivity and specificity of the thromboembolism RAM based on instances of thromboembolism in patients not receiving enoxaparin.

Those 18 years and older with a life expectancy of at least 6 months were eligible for enrollment prior to beginning systemic anticancer therapy with or without radiotherapy for GI or lung cancer.

The trial included a total of 328 patients, 128 of whom were classified as low risk, 100 who were high risk and assigned to enoxaparin, and 100 who were high risk and assigned to receive no thromboprophylaxis. The median patient age was 65 years (range, 30-88). Additionally, most patients were male (54%), White (92%), and had GI cancer (61%). Investigators reported that baseline characteristics were comparable between the randomized arms, although those in the low-risk group had higher rates of GI cancer diagnoses (73%) and nonmetastatic disease (72%).

Investigators reported major bleeding in 6 patients, including 1 receiving enoxaparin, 2 in the high-risk control group, and 3 in the low-risk group (P = .88). Additionally, there were no statistically significant differences in major and clinically relevant nonmajor bleeding events between the high-risk enoxaparin and control groups (HR, 2.21; 95% CI, 0.20-24.44).

Reference

Alexander M, Harris S, Underhill C, et al. Risk-directed ambulatory thromboprophylaxis in lung and gastrointestinal cancers: the TARGET-TP randomized clinical trial. JAMA Oncol. Published online September 21, 2023. doi:10.1001/jamaoncol.2023.3634