Risk-Directed Thromboprophylaxis Reduced Thromboembolism and Mortality Among Patients With Gastrointestinal and Lung Cancer

Using a biomarker-driven, risk-directed primary thromboprophylaxis approach for patients with gastrointestinal and lung cancer, thrombosis rates among patients with high-risk profiles were mitigated to those comparable to rates among patients with low-risk profiles, without additional safety concerns.

While thromboprophylaxis for patients in systemic anticancer treatment has been effective, existing risk models to maximize benefits underperform among patients with lung and gastrointestinal cancers. The TARGET-TP trial sought to assess the benefits and safety of biomarker-driven thromboprophylaxis while also externally validating a biomarker thrombosis risk assessment model in this patient population.

In this open-label, phase 3 trial, 328 patients with gastrointestinal and lung cancers who were initiating on systemic anticancer therapies were enrolled between June 2018 and July 2021. Of the patients enrolled, 201 had gastrointestinal cancer and 127 had lung cancer; 132 had metastatic disease. Using a thromboembolism risk assessment based on fibrinogen and D-dimer levels, patients were stratified into either low-risk or high-risk cohorts. Those in the high-risk group (n = 200) were randomized on a 1-to-1 basis to receive either 40 mg enoxaparin daily for 90 days (n = 100) or no thromboprophylaxis (n = 100, control). The low-risk group (128) underwent observation only. The primary outcome was objectively confirmed thromboembolism at 180 days, with key secondary outcomes including bleeding, survival, and risk model validation.

In the high-risk cohort, 8 patients in the enoxaparin group experienced thromboembolism compared with 23 patients in the control group (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.15 to 0.70; P = .005). In the low-risk group, 10 patients experienced a thromboembolism (high-risk control vs low-risk: HR, 3.33; 95% CI, 1.58 to 6.99; P = .002). The sensitivity of the risk model was 70% and the specificity was 61%. Major bleeding occurred in 1 patient in the enoxaparin group, 2 in the high-risk control group, and 3 in the low-risk group (P = .88). The 6-month mortality was 13% in the enoxaparin group vs 26% in the high-risk control group (HR, 0.48; 95% CI, 0.24 to 0.93; P = .03) and 7% in the low-risk group (vs high risk control: HR, 4.71; 95% CI, 2.13 to 10.42, P < .001).

Dr Alexander et al concluded, “risk-directed thromboprophylaxis reduced thromboembolism with a desirable number needed to treat, without safety concerns, and with reduced mortality,” adding “individuals at low risk avoided unnecessary intervention.”

Source:

Alexander M, Harris S, Underhill S, 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