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Risk-Directed Ambulatory Thromboprophylaxis in Lung and Gastrointestinal Cancers: The TARGET-TP Randomized Clinical Trial.
Alexander, Marliese; Harris, Sam; Underhill, Craig; Torres, Javier; Sharma, Sharad; Lee, Nora; Wong, HuiLi; Eek, Richard; Michael, Michael; Tie, Jeanne; Rogers, Jennifer; Heriot, Alexander G; Ball, David; MacManus, Michael; Wolfe, Rory; Solomon, Benjamin J; Burbury, Kate.
Affiliation
  • Alexander M; Department of Pharmacy, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Harris S; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
  • Underhill C; Bendigo Cancer Centre, Bendigo Health, Bendigo, Victoria, Australia.
  • Torres J; Border Medical Oncology and Haematology Research Unit, Albury Wodonga Regional Cancer Centre, Albury Wodonga, New South Wales, Australia.
  • Sharma S; University of New South Wales, Rural Medical School, Albury Campus, Sydney, New South Wales, Australia.
  • Lee N; Peter Copulos Cancer and Wellness Centre, Goulburn Valley Health, Shepparton, Victoria, Australia.
  • Wong H; Rural Clinical School-Shepparton, The University of Melbourne, Shepparton, Victoria, Australia.
  • Eek R; Ballarat Regional Integrated Cancer Centre, Grampians Health, Ballarat, Victoria, Australia.
  • Michael M; Bendigo Cancer Centre, Bendigo Health, Bendigo, Victoria, Australia.
  • Tie J; Department of Clinical Haematology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Rogers J; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Heriot AG; The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
  • Ball D; Border Medical Oncology and Haematology Research Unit, Albury Wodonga Regional Cancer Centre, Albury Wodonga, New South Wales, Australia.
  • MacManus M; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
  • Wolfe R; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Solomon BJ; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
  • Burbury K; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
JAMA Oncol ; 9(11): 1536-1545, 2023 Nov 01.
Article in En | MEDLINE | ID: mdl-37733336
ABSTRACT
Importance 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.

Objective:

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. Design, Setting, and

Participants:

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.

Interventions:

High-risk patients were randomized 11 to receive enoxaparin, 40 mg, subcutaneously daily for 90 days (extending up to 180 days according to ongoing risk) or no thromboprophylaxis (control). Main Outcomes and

Measures:

The primary outcome was objectively confirmed thromboembolism at 180 days. Key secondary outcomes included bleeding, survival, and risk model validation.

Results:

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). Conclusions and Relevance 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. Trial Registration ANZCTR Identifier ACTRN12618000811202.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Thrombosis / Venous Thromboembolism / Gastrointestinal Neoplasms Type of study: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Humans / Male Language: En Journal: JAMA Oncol Year: 2023 Document type: Article Affiliation country: Australia

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Thrombosis / Venous Thromboembolism / Gastrointestinal Neoplasms Type of study: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Humans / Male Language: En Journal: JAMA Oncol Year: 2023 Document type: Article Affiliation country: Australia