No Impact of Low Molecular Weight Heparin in Localised Lung Cancer

A randomized phase III controlled trial doesn’t show impact on overall and recurrence-free survival in patients with completely resected stage I-IIIA NSCLC

A randomised phase III controlled trial conducted in multiple institutions in France shows no impact of adjuvant low molecular weight heparin, tinzaparin at a dose of 100 IU/kg/day for 12 weeks on overall survival (OS) and recurrence-free survival in patients with completely resected stage I-IIIA non-small cell lung cancer (NSCLC). The study was presented by Dr Benjamin Besse of the Department of Cancer Medicine, Gustave Roussy Institut de Cancérologie, Villejuif, France during the ESMO Asia 2017 in Singapore, an Annual Congress organised by the European Society for Medical Oncology. 

The study team explained in background that whether low molecular weight heparin impact the survival of cancer patients remains controversial. Experiments suggest that low molecular weight heparin inhibits tumour growth and metastasis. Studies in humans suggest that low molecular weight heparin is associated with a higher survival in patients with cancer related thrombosis. Two recent studies suggest that low molecular weight heparin may increase the survival of patients with cancer who do not have an associated thrombosis. The purpose of the study was to assess the effect of low molecular weight heparin on the OS of patients with resected early-stage NSCLC.

From August 2007 to June 2013, the French investigators randomised 549 patients to tinzaparin (n = 269) or control (n = 280). A total of 359 (65.4%) and 190 (34.6%) patients had stage I and II-III disease, respectively, and 220 patients (40.1%) received adjuvant chemotherapy. Median follow-up was 5.7 years.

There was no significant difference in OS between groups (Hazard Ratio [HR], 1.24; 95% Confidence Interval [CI], 0.92 to 1.68; p = 0.17). Five-year OS was 74.2% (95% CI, 68.9% to 79.9%) and 68.2% (95% CI, 62.5% to 74.4%) in the control and tinzaparin groups, respectively. There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94; 95% CI, 0.68 to 1.30; p = 0.70). In patients who received adjuvant chemotherapy, OS was lower in the tinzaparin group (HR, 1.78; 95%CI, 1.13 to 2.81; p = 0.013).

Two patients in the tinzaparin group experienced serious bleeding during the treatment period.

These results suggest that clinical studies of heparins as antitumour agents may no longer be considered a relevant approach.

The study NCT00475098 was funded by French Ministry of Health (PHRC AOM05185 and PHRC AOM12612). Leo Pharma provided the study drug and a complementary grant but had no role in study design, conduct of the study, and the data analysis.

Reference

397O - B. Besse, et al. Antitumoral Effect of Low Molecular Weight Heparin in Localized Lung Cancer. A randomized phase III controlled trial.