Low-Molecular-Weight Heparin as Adjuvant Therapy in Small-Cell Lung Cancer − Results of the RASTEN Study

Prothrombotic State in Cancer

Cancer is typically considered a procoagulant state, and thromboembolic disease is a significant cause of morbidity and mortality in oncology patients. Anticoagulants are used to treat thromboembolic events. According to some meta-analyses, lower mortality was observed in some cancer patients treated with low-molecular-weight heparin (LMWH) compared to those receiving warfarin. The possible antitumor effect is attributed to the ability of LMWH to inhibit angiogenesis and metastasis.

According to conclusions from a Cochrane Database meta-analysis, this effect of LMWH on one-year survival in oncology patients without therapeutic or prophylactic indication for anticoagulant therapy was observed only in patients diagnosed with small-cell lung cancer (SCLC). SCLC accounts for 15% of lung cancers and is characterized by neuroendocrine activity, early metastasis, and poor prognosis.

Course and Goals of the RASTEN Study

Individual LMWH preparations have similar anticoagulant effects but different pharmacological properties and may therefore differently influence tumor growth. The randomized, open, multicenter RASTEN study aimed to assess the antitumor effect of enoxaparin in patients with SCLC. A total of 186 patients with newly diagnosed SCLC received enoxaparin in a supraprophylactic dose (1 mg/kg daily) alongside standard therapy, while 191 patients were treated with standard therapy alone.

The primary goal of the study was to compare overall survival, while secondary goals included comparing the incidence of thromboembolic and bleeding events and time to disease progression.

Results

Although enoxaparin administration significantly reduced the incidence of thromboembolic events (hazard ratio [HR] 0.31; 95% confidence interval [CI] 0.11–0.84; p = 0.02) and fatal bleeding events occurred in both groups, no effect of enoxaparin on overall survival (HR 1.11; 95% CI 0.89–1.38; p = 0.36) or time to disease progression (HR 1.18; 95% CI 0.95–1.46; p = 0.14) was demonstrated.

Conclusion and Clinical Recommendation

Based on the results of this study, adding enoxaparin to the standard SCLC therapy cannot be recommended for individuals without an anticoagulant therapy indication for prophylaxis or treatment of thromboembolic events, as its use does not impact the survival of patients with this disease. However, the study clearly confirmed the ability of enoxaparin to reduce the risk of thromboembolic events in patients with SCLC.

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Source: Ek L., Gezelius E., Bergman B. et al. Randomized phase III trial of low-molecular-weight heparin enoxaparin in addition to standard treatment in small-cell lung cancer: the RASTEN Trial. Ann Oncol 2018; 29 (2): 398–404, doi: 10.1093/annonc/mdx716.