对接受全身抗癌治疗的个体进行抗血栓预防已被证明是有效的。最大化效益的潜力依赖于改进的风险导向策略，但现有风险模型在肺癌和胃肠癌人群中表现不佳。评估肺癌和胃肠癌患者进行生物标志物驱动的抗血栓预防的临床益处和安全性，并对生物标志物血栓风险评估模型进行外部验证。本开放标签、3期随机临床试验（接受抗癌治疗的门诊患者靶向抗血栓预防[TARGET-TP]）由澳大利亚1个大都市和4家地区医院于2018年6月至2021年7月（6个月为初级随访期）进行。纳入年满18周岁或以上的肺癌或胃肠癌患者进行全身抗癌治疗。基于纤维蛋白原和D-二聚体水平的血栓栓塞风险评估将个体分为低风险（观察）和高风险（随机）队列。高风险患者1:1随机分组接受皮下注射40毫克速碧林，每天一次，共90天（根据持续风险延伸至180天）或无抗血栓预防（对照组）。主要结局为180天内客观确认的血栓栓塞。主要次要结果包括出血、生存和风险模型验证。在符合条件的782名成年患者中，有328名（42%）被纳入试验（年龄中位数65岁[范围30-88岁]；男性176名[54%]）。这些参与者中，201名（61%）患有胃肠癌，127名（39%）患有肺癌，132名（40%）有转移性疾病；200名（61%）为高风险（各组100名），128名（39%）为低风险。在高风险队列中，接受速碧林随机分组的8名个体（8%）和对照组23名个体（23%）发生血栓栓塞（风险比[HR] 0.31；95% CI，0.15-0.70；P = .005；需治疗人数为6.7）。低风险个体有10例（8%）发生血栓栓塞（高风险对照 vs 低风险：HR，3.33；95% CI，1.58-6.99；P = .002）。风险模型的敏感性为70%，特异性为61%。大出血率较低，速碧林组有1名参与者（1%），高风险对照组2名（2%），低风险组3名（2%）发生（P = .88）。6个月死亡率速碧林组为13%，高风险对照组为26%（HR，0.48；95% CI，0.24-0.93；P = .03），低风险组为7%（与高风险对照相比：HR，4.71；95% CI，2.13-10.42；P < .001）。本随机临床试验对肺癌和胃肠癌个体根据血栓风险评分进行分层，并根据风险进行血栓预防，减少了血栓栓塞发生率，需要治疗的人数合理，无安全顾虑，且降低了死亡率。低风险个体避免了不必要的干预。研究结果表明，在这个人群中，基于生物标志物的风险导向主要抗血栓预防是合适的方法。ANZCTR标识符：ACTRN12618000811202。

Thromboprophylaxis for individuals receiving systemic anticancer therapies has proven to be effective. Potential to maximize benefits relies on improved risk-directed strategies, but existing risk models underperform in cohorts with lung and gastrointestinal cancers.To assess clinical benefits and safety of biomarker-driven thromboprophylaxis and to externally validate a biomarker thrombosis risk assessment model for individuals with lung and gastrointestinal cancers.This open-label, phase 3 randomized clinical trial (Targeted Thromboprophylaxis in Ambulatory Patients Receiving Anticancer Therapies [TARGET-TP]) conducted from June 2018 to July 2021 (with 6-month primary follow-up) included adults aged 18 years or older commencing systemic anticancer therapies for lung or gastrointestinal cancers at 1 metropolitan and 4 regional hospitals in Australia. Thromboembolism risk assessment based on fibrinogen and d-dimer levels stratified individuals into low-risk (observation) and high-risk (randomized) cohorts.High-risk patients were randomized 1:1 to receive enoxaparin, 40 mg, subcutaneously daily for 90 days (extending up to 180 days according to ongoing risk) or no thromboprophylaxis (control).The primary outcome was objectively confirmed thromboembolism at 180 days. Key secondary outcomes included bleeding, survival, and risk model validation.Of 782 eligible adults, 328 (42%) were enrolled in the trial (median age, 65 years [range, 30-88 years]; 176 male [54%]). Of these participants, 201 (61%) had gastrointestinal cancer, 127 (39%) had lung cancer, and 132 (40%) had metastatic disease; 200 (61%) were high risk (100 in each group), and 128 (39%) were low risk. In the high-risk cohort, thromboembolism occurred in 8 individuals randomized to enoxaparin (8%) and 23 control individuals (23%) (hazard ratio [HR], 0.31; 95% CI, 0.15-0.70; P = .005; number needed to treat, 6.7). Thromboembolism occurred in 10 low-risk individuals (8%) (high-risk control vs low risk: HR, 3.33; 95% CI, 1.58-6.99; P = .002). Risk model sensitivity was 70%, and specificity was 61%. The rate of major bleeding was low, occurring in 1 participant randomized to enoxaparin (1%), 2 in the high-risk control group (2%), and 3 in the low-risk group (2%) (P = .88). Six-month mortality 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) and 7% in the low-risk group (vs high-risk control: HR, 4.71; 95% CI, 2.13-10.42; P < .001).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.ANZCTR Identifier: ACTRN12618000811202.