Survival benefit with low-molecular-weight heparin in patients with advanced solid tumors: A post hoc analysis of PROTECHT trial.

9640 Background: Use of low molecular weight heparin (LMWH) are approved to reduce the thromboembolic events in patients with solid tumors. The effect of LMWH on overall survival (OS) has been debated but not demonstrated, and current guidelines recommend against its use to increase OS. We have conducted a post hoc analysis of PROTECHT (PROphylaxis of ThromboEmbolism during CHemoTherapy) randomized study that compared nadroparin to placebo in patients with metastatic or locally advanced solid tumors. Methods: In our post-hoc analysis, individual patient data (n=1,150) was reviewed and analyzed to assess response to chemotherapy and overall survival. Tumor response to chemotherapy was assessed using Response Evaluation Criteria in Solid Tumors. Survival analysis was performed through a Cox regression model with treatment, response to chemotherapy and their interaction term (treatment-by- response to chemotherapy) as covariates. A statistically significant interaction indicates that an overall comparison between the two treatments is inappropriate, and therefore hazard ratios (HRs) with associated 95% CI and p-values must be evaluated separately in each group (disease control / no disease control). Results: A statistically significant interaction between treatment and response to chemotherapy (P=0.0435) was found, suggesting the hypothesis that OS treatment difference depends on the response to chemotherapy. A statistically significant difference in OS in favour of nadroparin treatment was found in the subgroup of patients with disease control (HR=0.665 [95%CI 0.442 - 1.00], P=0.05), but not in the subgroup of patients without disease control (HR=1.077 [95%CI 0.857 - 1.35], P=0.525). In patients with disease control, 1-year survival rate was 83% [95%CI 79% - 87%] in nadroparin and 76% [95%CI 70% - 83%] in placebo respectively; conversely in patients without disease control 1-year OS was 49% [95%CI 44% - 53%] in nadroparin and 51% [95%CI 45% - 58%] in placebo. Conclusions: this post hoc analysis support the hypothesis that LMWH could increase survival albeit limited to patients responding to chemotherapy. Clinical trial information: NCT 00951574.