Pooled analysis of individual patient-level data from all randomized, double-blind, placebo-controlled trials of darbepoetin alfa in the treatment of patients with chemotherapy-induced anemia.

PURPOSE Although numerous clinical trials have demonstrated the efficacy and tolerability of erythropoiesis-stimulating agents (ESAs) in patients with chemotherapy-induced anemia (CIA), results of some recent trials and one meta-analysis have suggested that ESAs may negatively impact survival and/or disease control in patients with cancer. METHODS To assess the benefits and risks of ESAs in CIA, we conducted a pooled analysis of individual patient-level data from all randomized, double-blind, placebo-controlled trials in 2,122 patients with CIA receiving darbepoetin alfa (DA; n = 1,200) or placebo (n = 912). RESULTS DA did not increase mortality (hazard ratio = 0.97; 95% CI, 0.85 to 1.1) and had no effect on progression-free survival (hazard ratio = 0.93; 95% CI, 0.84 to 1.04) and disease progression (hazard ratio = 0.92; 95% CI, 0.82 to 1.03), but, as expected, increased the risk for thromboembolic events (hazard ratio = 1.57; 95% CI, 1.10 to 2.26). Overall and progression-free survival were not affected by baseline hemoglobin and seemed better in patients who achieved hemoglobin more than 12 or more than 13 g/dL. Transfusions and rates of hemoglobin increase (> 1 g/dL in 14 days; > 2 g/dL in 28 days) owing to transfusions were associated with an increased risk for death and disease progression in both treatment groups; in the absence of transfusions, rates of hemoglobin increase did not appear to increase the risk for adverse outcomes. Compared with placebo, DA significantly reduced the risk of receiving one or more transfusion. CONCLUSION There seemed to be no association between DA and risk of death or disease progression in this meta-analysis of individual patient data from DA studies conducted in CIA, the approved indication for ESAs in oncology.