Darbepoetin alfa for treating chemotherapy-induced anemia in patients with a baseline hemoglobin level or = 10 g/dL: an exploratory analysis from a randomized, double-blind, active-controlled trial

Abstract

Background: Several studies have shown that darbepoetin alfa, an erythropoiesis-stimulating agent (ESA), can reduce transfusions and increase hemoglobin (Hb) levels in patients with chemotherapy-induced anemia (CIA). Recent safety concerns, however, have prompted changes to ESA product information. In the European Union and United States, ESA therapy initiation for CIA is now recommended at a Hb level < or = 10 g/dL. The present exploratory analysis examined how ESA initiation at this Hb level may impact patient care.

Methods: Data from a phase 3 randomized trial were retrospectively reanalyzed. CIA patients with nonmyeloid malignancies were randomized 1:1 to 500 mcg darbepoetin alfa every three weeks (Q3W) or 2.25 mcg/kg darbepoetin alfa weekly (QW) for 15 weeks. A previously published report from this trial showed Q3W dosing was non-inferior to QW dosing for reducing transfusions from week 5 to end-of-the-treatment period (EOTP). In the present analysis, outcomes were reanalyzed by baseline Hb <10 g/dL and > or = 10 g/dL. Endpoints included transfusion rates, Hb outcomes, and safety profiles.

Results: This study reanalyzed 351 and 354 patients who initiated ESA therapy at a baseline Hb of <10 g/dL or > or = 10 g/dL, respectively. From week 5 to EOTP, the estimated Kaplan-Meier transfusion incidence (Q3W vs QW) was lower in the > or = 10 g/dL baseline-Hb group (14% vs 21%) compared with the <10 g/dL baseline-Hb group (36% vs 41%). By week 5, the > or = 10 g/dL baseline-Hb group, but not the <10 g/dL baseline-Hb group, achieved a mean Hb > or = 11 g/dL. The Kaplan-Meier estimate of percentage of patients (Q3W vs QW) who achieved Hb > or = 11 g/dL from week 1 to EOTP was 90% vs 85% in the > or = 10 g/dL baseline-Hb group and 54% vs 57% in the <10 g/dL baseline-Hb group. Both baseline-Hb groups maintained mean Hb levels <12 g/dL and had similar safety profiles, though more patients in the > or = 10 g/dL baseline-Hb group reached the threshold Hb of > or = 13 g/dL.

Conclusion: In this exploratory analysis, darbepoetin alfa Q3W and QW raised Hb levels and maintained mean Hb at <12 g/dL in both baseline-Hb groups. The > or = 10 g/dL baseline-Hb group had fewer transfusions and faster anemia correction. Additional studies should prospectively evaluate the relationship between Hb levels at ESA initiation and outcomes.

Trial registration: ClinicalTrials.gov Identifier NCT00118638.

Figures

Figure 1

Hemoglobin profile over the treatment period. The mean hemoglobin (Hb) concentration (g/dL) is shown over time in weeks. The treatment period lasted through the earlier of day 109 or end of study. Error bars represent the 95% confidence intervals. The dotted, black horizontal line marks the 11 g/dL Hb level on the Y axis, and the dotted, black vertical line marks week 5 on the X axis. A. Patients with a baseline Hb level < 10 g/dL. B. Patients with a baseline Hb level ≥10 g/dL

Figure 2

Time to hemoglobin concentration ≥10 g/dL for patients with baseline hemoglobin < 10 g/dL. Hemoglobin (Hb) measurements within 28 days of a red blood cell transfusion or whole blood transfusion were excluded. Patients not achieving a Hb level ≥10 g/dL between day 1 and end of the treatment period (EOTP, earlier of day 109 or end of study) were censored at their last Hb measurement prior to EOTP.

Figure 3

Time to a hemoglobin concentration ≥11 g/dL. Hemoglobin (Hb) measurements within 28 days of a red blood cell transfusion or whole blood transfusion were excluded. Patients not achieving a Hb level ≥11 g/dL between day 1 and end of the treatment period (EOTP, earlier of day 109 or end of study) were censored at their last Hb measurement prior to EOTP. Two patients in the ≥10 g/dL baseline-Hb group who had a baseline Hb level ≥11 g/dL were excluded from the analysis. A. Patients with a baseline Hb level < 10 g/dL. B. Patients with a baseline Hb level ≥10 g/dL.