UK Trial Shows No Survival Benefit of Low–Molecular-Weight Heparin in Patients With Lung Cancer
In the UK phase III FRAGMATIC trial reported in the Journal of Clinical Oncology, Macbeth et al found no survival benefit of adding low–molecular-weight heparin to standard treatment in patients with lung cancer. Previous evidence suggested that low–molecular-weight heparin might improve survival in cancer patients by preventing venous thromboembolism and progression of metastases. The UK trial was aimed at enrolling a large enough patient population to demonstrate a survival difference in a single type of cancer.
Study Details
In the open-label trial, 2,202 patients with newly diagnosed lung cancer of any stage and histology from 129 sites in the UK were randomized between September 2007 and December 2011 to receive low–molecular-weight heparin (n = 1,101) or no low–molecular-weight heparin (n = 1,101). Low–molecular-weight heparin consisted of dalteparin (Fragmin) at 5,000 IU given subcutaneously daily for a maximum of 24 weeks. Randomization was stratified by intended first treatment, type of cancer (small cell or non–small cell), sex, performance status, presence of metastases, and treatment center. The primary outcome was 1-year survival.
Survival
Data were analyzed after 2,013 of 2,047 deaths intended for the primary analysis. Overall, 88% of deaths were due to lung cancer. Median follow-up was 23.1 months in surviving patients. One-year overall survival was 41.3% in the low–molecular-weight heparin group vs 42.5% in the no low–molecular-weight heparin group, yielding a hazard ratio (HR) of 1.01 (P = .814); the result was similar after adjustment for stratification factors (HR = 1.02, P = .66). Median overall survival was 9.8 vs 10.2 months. One-year metastasis-free survival was 16.2% vs 14.9% (HR = 0.99, P = .86).
Venous Thromboembolism and Bleeding
Risk of venous thromboembolism was significantly reduced in the low–molecular-weight heparin group (5.5% vs 9.7%, HR = 0.57, P = .001). There was no difference between groups in major bleeding events during the study treatment period (1.1% vs 0.7%), but a higher incidence of the composite of major and clinically relevant nonmajor bleeding events was observed in the low–molecular-weight heparin group (5.6% vs 1.3%).
The investigators concluded: “Low–molecular-weight heparin did not improve overall survival in the patients with lung cancer in this trial. A significant reduction in venous thromboembolism is associated with an increase in clinically relevant nonmajor bleeding. Strategies to target those at greatest risk of venous thromboembolism are warranted.”
The study was supported by Cancer Research UK, Pfizer, and the National Institute for Health Research Cancer Network.
Fergus Macbeth, DM, of Wales Cancer Trials Unit, Cardiff University, is the corresponding author of the Journal of Clinical Oncology article.
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