Enoxaparin in SCLC Reduces VTE, but Fails to Improve Survival

Treatment with the low molecular weight heparin (LMWH) enoxaparin failed to improve overall or progression-free survival outcomes in patients with small-cell lung cancer (SCLC), in spite of an improvement in rates of venous thromboembolism (VTE), according to a new study.

“VTE is a well-recognized complication in malignancy and a major contributor to cancer-associated mortality and morbidity,” wrote study authors led by Mattias Belting, MD, PhD, of Lund University in Sweden. Research has yielded conflicting results, however, on whether LMWH therapy might improve survival by reducing VTE incidence.

The RASTEN trial was an open-label randomized study that included 390 patients (377 eligible for the intention-to-treat population) with newly diagnosed SCLC. Patients were randomized to receive either enoxaparin at a supraprophylactic dose of 1 mg/kg (186 patients), or to a control group (191 patients). The median follow-up period was 41 months for patients still alive, and the results were published in Annals of Oncology.

There was no difference in the primary outcome of overall survival (OS). The median OS was 10.6 months with enoxaparin, and 11.3 months without it, for a hazard ratio (HR) of 1.11 (95% CI, 0.89–1.38; P = .36). An analysis that stratified the results for study center and adjusted for age, gender, disease stage, and performance status did not dramatically change the results, with an HR of 1.14 (95% CI, 0.91–1.45; P = .26). At 1 year, the survival rate with the LMWH agent was 48% and 47% without it, for an HR of 0.98 (95% CI, 0.74–1.30; P = .92).

The median OS in patients with limited disease was 17.8 months, and in those with extensive disease it was 8.6 months; there were no differences between treatment arms in either of these subgroups. Enoxaparin also had no effect on progression-free survival, with an HR of 1.18 (95% CI, 0.95–1.46; P = .14).

This lack of difference in survival outcomes was seen in spite of significant differences in VTE rates. Sixteen control patients (8.4%) developed a VTE, compared with only five enoxaparin patients (2.7%; P = .02). Two of the control patients developed fatal pulmonary embolization. The cumulative incidence of VTE at 6 months was 2.5% with enoxaparin, and 8.5% without it, for an HR of 0.31 (95% CI, 0.11–0.84; P = .02).

There were 27 hemorrhagic events in the enoxaparin group, compared with 8 in the control group; most of these were considered clinically non-relevant. Three patients in the enoxaparin group and one in the control group suffered fatal pulmonary hemorrhages.

The authors speculated that the lack of effect in spite of reduced systemic thrombosis may be due to “poor distribution to the procoagulant, hypoxic tumor niche,” or to the inability of LMWH agents to target coagulation-dependent signaling.

“At present, the use of LMWH in cancer includes primary prophylaxis in patients at high risk of VTE, in patients diagnosed with VTE, and as secondary prophylaxis,” they wrote. “The present study provides strong support against a more general use of LMWH as a tumor-inhibiting agent, and underlines the need for risk biomarkers to guide clinicians in tailoring individualized LMWH treatment.”