Early hemoglobin decline and survival prognosis in epoetin alfa studies

Abstract

9625 Background: When cancer patients (pts) with chemotherapy-induced anemia (CIA) respond to erythropoietic-stimulating agents (ESA), hemoglobin (Hb) typically increases within 4–8 weeks. This exploratory analysis examined whether mortality differs depending on Hb response after 4 or 8 weeks of epoetin alfa (EPO) treatment or depending on transfusion. Methods: Pt-level data were analyzed from 31 randomized studies (7,215 pts) of epoetin alfa vs non-EPO (15 studies) or placebo (16 studies) in pts with CIA. A landmark analysis was used; Hb change was set at a specific time (4 and 8 weeks) and subsequent survival was examined separately for EPO and placebo. Pts were categorized as “Hb increased” (>0.5 g/dL), “Hb decreased” (>0.5 g/dL), or “Hb stable” (within ±0.5 g/dL) compared to baseline. Hb stable was compared to other Hb change categories with Cox proportional hazards models, stratified by study and adjusted for potential confounders. Results: The hazard ratio (HR) for Hb decreased versus Hb stable at 4 weeks was 1.44 for EPO (95% CI: 1.04, 1.99), indicating worse survival for pts with a decline in Hb. This association was weaker for placebo (HR: 1.12; 95% CI: 0.74, 1.67). Increased risk with declining Hb in EPO-treated pts was most pronounced in studies that maintained Hb ≥12 g/dL or treated pts for >12–16 weeks (1,876 pts). Patterns were similar using the 8-week landmark. In both EPO-treated and placebo pts, transfusion increased the rate of on-study death ∼3.5 fold (treating transfusion as a time-dependent variable). Conclusions: These exploratory findings suggest that both decreased Hb after 4 or 8 weeks of EPO treatment and transfusion are associated with increased risk of death. In spite of adjustment for other prognostic factors, it is likely that this association reflects poorer underlying prognosis of pts whose Hb fails to respond. ESAs should be discontinued in the absence of a Hb response. [Table: see text]