medwireNews: Findings from the TARGET-TP trial support a biomarker-driven, risk-directed approach to primary thromboprophylaxis in ambulatory patients with gastrointestinal or lung cancer receiving systemic anticancer treatment.
The approach “reduced thromboembolism with a desirable number needed to treat, without safety concerns, and with reduced mortality,” say Marliese Alexander (Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia) and team in JAMA Oncology.
They add: “Future investigations in expanded tumor groups that incorporate clinician and consumer preference for choice of anticoagulant are warranted.”
The author of a related commentary says that although the trial has limitations, such as the small sample size making it “underpowered to assess for true differences in bleeding rates,” the results “are both consistent with and meaningfully add to the existing evidence base.”
Alok Khorana (Cleveland Clinic Taussig Cancer Institute, Ohio, USA) therefore believes that the biggest question in the field “is not which risk-based approach or which anticoagulant is the best for primary prevention,” but “what is stopping patients with cancer from being offered thromboprophylaxis in the first place?”
And he calls for more implementation science “to translate the findings of RCTs [randomized clinical trials] to the clinic so that stellar efforts such as those by the investigators of TARGET-TP truly lead to a reduction in the public health burden of [venous thromboembolism] in people with cancer.”
The 328 participants (54% men) of the phase 3 trial – who were aged a median of 65 years and had either gastrointestinal (61%) or lung (39%) cancer – underwent an assessment of fibrinogen and D-dimer levels before initiating anticancer therapy and after one cycle of treatment.
Of these, 200 individuals were classed as having a high thromboembolic risk and were randomly assigned to either receive subcutaneous enoxaparin 40 mg/day for at least 90 days, with an extension up to 180 days permitted based on ongoing risk, or no thromboprophylaxis. The remaining 128 participants were low risk and formed an observational cohort.
By the 180-day follow-up, a symptomatic or incidental thromboembolic event (deep vein thrombosis, pulmonary embolism, or arterial thromboembolism) had occurred in 8% of the 100 patients in the enoxaparin group and 23% of the 100 in the control group. This equated to an absolute risk reduction of 15% and a relative risk reduction of 65% with the use of enoxaparin. The number needed to treat to prevent one thromboembolic event was 6.7.
The incidence of thromboembolism in the low-risk cohort was 8%, which the researchers say is “higher than the idealistic net 0 target,” but “it represents a clinically acceptable risk threshold in the absence of a treat-all approach.”
There was no significant difference between the groups with respect to the incidence of major bleeding, which occurred in 1% of the enoxaparin group, 2% of the high-risk no treatment group, and 2% of the low-risk group.
The use of enoxaparin was associated with a significant decrease in 6-month all-cause mortality, at a rate of 13% versus 26% with no prophylaxis, which equated to a 52% reduction in the risk for death with thromboprophylaxis.
The 6-month mortality rate in the low-risk cohort was 7%, and the mortality risk was significantly lower than that in the high-risk control group.
The commentator says that “[t]he striking association of thromboprophylaxis with reduced mortality is […] certainly deserving of further study.”
He continues: “However, as the authors note, these findings are inconsistent with several large prior RCTs, including those expressly designed to evaluate the effect of [low-molecular-weight heparins] on mortality in people with cancer and require additional confirmation.”
Alexander and colleagues also evaluated the performance of the risk assessment model, finding a sensitivity of 70% and a specificity of 61%, which they admit “ideally should have been higher.” But they believe that compared with other available models, “it is potent and ready for scaled implementation with a routine test available in diagnostic pathology laboratories.”
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