Journal Article

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

Bridges, Ken, Ludwig, Heinz, Hedenus, Michael, Vermorken, Jan, Pujol, Beatriz, Vansteenkiste, Johan, Gascon, Pere, Hamilton, Lisa, Bokemeyer, Carsten

2009

Overview

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 ≤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 ≥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 ≥10 g/dL, respectively. From week 5 to EOTP, the estimated Kaplan-Meier transfusion incidence (Q3W vs QW) was lower in the ≥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 ≥10 g/dL baseline-Hb group, but not the <10 g/dL baseline-Hb group, achieved a mean Hb ≥11 g/dL. The Kaplan-Meier estimate of percentage of patients (Q3W vs QW) who achieved Hb ≥11 g/dL from week 1 to EOTP was 90% vs 85% in the ≥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 ≥10 g/dL baseline-Hb group reached the threshold Hb of ≥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 ≥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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Aged / Aged, 80 and over / Anemia / Anemia - chemically induced / Anemia - drug therapy / Anemia - metabolism / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Cancer therapies / Care and treatment / Chemotherapy / Clinical Trials, Phase III as Topic / Complications and side effects / Confidence intervals / Darbepoetin alfa / Data collection / Diagnosis / Dosage and administration / Double-Blind Method / Drug-Related Side Effects and Adverse Reactions / Erythropoietin - analogs & derivatives / Erythropoietin - therapeutic use / Female / Health aspects / Health Promotion and Disease Prevention / Hematinics - therapeutic use / Hemoglobins - metabolism / Hospitals / Humans / Male / Medicine/Public Health / Meta-analysis / Middle Aged / Mortality / Multicenter Studies as Topic / Oncology / Radiation therapy / Randomized Controlled Trials as Topic / Research Article / Retrospective Studies / Risk factors / Surgical Oncology / Treatment Outcome / Young Adult