Author of

• 20164

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  P1.15 - SCLC/Neuroendocrine Tumors (ID 701)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: SCLC/Neuroendocrine Tumors
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 22792

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    P1.15-007 - Randomized Phase III Trial of Enoxaparin in Addition to Standard Treatment in Small Cell Lung Cancer: The RASTEN Trial (ID 9517)

    09:30 - 09:30  |  Author(s): J. Sundberg
    • Abstract

    Background:
    Hypercoagulation is a hallmark of cancer, and several coagulation factors contribute to tumor development and progression in addition to development of venous thromboembolism (VTE), which is a major cause of morbidity and mortality in lung cancer. Early studies suggested that coagulation inhibition with low molecular weight heparin (LMWH) may improve survival specifically in small cell lung cancer (SCLC) patients, whereas other studies showed contradictory results. The aim of RASTEN was to investigate the survival effect of LMWH enoxaparin in a trial powered to demonstrate a clinically significant difference in a homogenous group of SCLC patients. (ClinicalTrials.gov: NCT00717938)
    
    Method:
    We performed a randomized, multicenter, open-label trial to investigate the effect of LMWH enoxaparin administered at a supraprophylactic dose (1 mg/kg) and continuously during standard treatment in patients with newly diagnosed SCLC. The primary outcome was overall survival (OS), and secondary outcomes were progression free survival (PFS), incidence of VTE and hemorrhagic events.
    
    Result:
    In RASTEN, 390 patients were randomized over an 8-year period, of which 186 and 191 were included in the final analysis in the LMWH and control arm, respectively. We found no evidence of a difference in OS or PFS by the addition of enoxaparin (HR 1.11; 95% CI: 0.89-1.38, P=0.36, and HR 1.18; 95% CI: 0.95-1.46, P=0.14, respectively). Subgroup analysis of patients with limited and extensive disease did not show any reduction in mortality by enoxaparin. The incidence of VTE events was significantly reduced in the LMWH arm (HR 0.31; 95% CI: 0.11-0.84, P=0.02). Hemorrhagic events were more frequent in the LMWH-treated group but fatal bleedings occurred in both arms.
    
    Conclusion:
    Anticoagulants have previously been found to exert impressive tumor inhibiting properties in experimental models; however, results from clinical trials have been conflicting. This may partly be explained by the use of suboptimal, prophylactic LMWH dosages. In the present study, LMWH enoxaparin in addition to standard therapy did not improve OS in SCLC patients despite being administered at a supraprophylactic dose and despite resulting in a significant reduction in VTE incidence. Based on these results, the addition of LMWH cannot be generally recommended in the management of SCLC patients. Further, our data underline that predictive biomarkers of VTE and LMWH-associated bleeding are warranted for individualized anticoagulant therapy of cancer patients.