Heparin Fails to Improve Survival in Lung Cancer Patients

The use of low molecular-weight heparin (LMWH) failed to improve either metastasis-free or overall survival (OS) in newly diagnosed lung cancer patients, according to a large randomized phase III trial. There was a decrease in venous thromboembolism (VTE), though this corresponded to an increase in risk of clinically relevant non-major bleeding events.

“Evidence suggests LMWHs may have anti-metastatic properties, including inhibition of selectins, angiogenesis, endothelial adhesion, and tumor seeding and induction of tissue factor plasminogen inhibitor,” wrote study authors led by Fergus Macbeth, DM, of Cardiff University in Wales. Only small trials, though, have tested this hypothesis.

The new FRAGMATIC trial randomized 2,202 patients with lung cancer to either standard care plus a prophylactic dose of LMWH for 24 weeks or standard care alone; the patients were spread out between small-cell lung cancer and non–small-cell lung cancer (NSCLC), and across stages. The results were published online ahead of print in the Journal of Clinical Oncology.

The data in the study were analyzed prior to reaching the intended number of events (2,047 deaths intended, 2,013 deaths reached) after discussion with a data monitoring committee. At that point, there was no evidence of survival benefit with LMWH.

The median OS in the LMWH group was 9.8 months, compared with 10.2 months in the no-LMWH arm. At 1 year, the survival rates in the two groups were 41.3% and 42.5%, respectively. This yielded a hazard ratio (HR) for survival of 1.01 (95% confidence interval [CI], 0.93–1.10; P = 0.814).

The secondary endpoint, metastasis-free survival, was also similar between the groups. The HR for this endpoint was 0.99 (95% CI, 0.91–1.08; P = 0.86).

A total of 168 patients experienced a VTE; there were 61 in the LMWH patients (5.5%) and 107 in the no-LMWH group (9.7%). The 1-year VTE-free survival rates were 94.1% and 89.5%, respectively, for an HR of 0.57 (95% CI, 0.42–0.79; P < .001). There was a corresponding increased rate of hemorrhagic events during the trial period, with 5.6% of LMWH patients and 1.3% of no-LMWH patients experiencing a major or clinically relevant non-major bleeding event.

“Previous studies have suggested heparins might have anti-metastatic effects, but we found no difference in metastasis-free survival between the two arms,” the researchers wrote. This could be a result of having too few patients with early-stage disease who might benefit from anti-metastatic effects. “Future studies in this and other tumor primaries may best focus on the early-stage cancers, in particular looking at patients undergoing resection and adjuvant chemotherapy.” The ongoing TILT study will explore the use of tinzaparin in only early-stage NSCLC patients undergoing resection.