title: Transfusion risk in cancer patients with chemotherapy-induced anemia when initiating darbepoetin alfa therapy at a baseline hemoglobin level of <9 g/dL versus 9 to <10 g/dL versus ≥ 10 g/dL: an exploratory analysis of a phase 3 trial.
abstract: Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anemia (CIA). Safety concerns have prompted changes to the ESA-product information, which now recommends initiating ESAs at hemoglobin (Hb) levels < 10 g/dL (US) or ≤ 10 g/dL (EU). The present exploratory analysis of a DA trial examined how baseline-Hb levels at ESA initiation affect transfusion rates, Hb response, and safety outcomes in CIA patients. Data were retrospectively analyzed from a phase 3 trial of CIA patients randomised to 500 mcg DA every 3 weeks (Q3 W) or to 2.25 mcg/kg DA weekly (QW) for 15 weeks. In the current analysis, data were reanalyzed by baseline-Hb categories of <9 g/dL (n = 126), 9 to <10 g/dL (n = 225), and ≥ 10 g/dL (n = 354). The Q3 W and QW groups were combined. Transfusion rates were highest in the <9 g/dL baseline-Hb group in all time periods examined. The Kaplan-Meier percentage (95% CI) of patients achieving Hb ≥ 10 g/dL was 68% (59, 78) and 88% (82, 92) in the <9 g/dL and 9 to <10 g/dL baseline-Hb groups, respectively. With lower baseline-Hb, incidence of a ≥ 1 g/dL-Hb rise in 14 days progressively decreased. Incidence of venous thromboembolic events was similar in all baseline-Hb groups and similar between patients with or without a ≥ 1 g/dL-Hb rise in 14 days. Overall, transfusion risk increased and Hb response decreased at lower baseline-Hb levels in this exploratory analysis. When following ESA-product information to initiate ESAs at Hb ≤ 10 g/dL, the greatest benefit may be achieved when initiating close to 10 g/dL. Prospective studies are needed to further examine this hypothesis.
authors.affiliation: Oncology-Hematology Department, Grand Hopital de Charleroi, 3 Grand Rue, 6000 Charleroi, Belgium. Canon.JL@ghdc.be
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Canon
authors.forename: Johan
authors.initials: J
authors.lastname: Vansteenkiste
authors.forename: Michael
authors.initials: M
authors.lastname: Hedenus
authors.forename: Pere
authors.initials: P
authors.lastname: Gascon
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.forename: Jan
authors.initials: J
authors.lastname: Vermorken
authors.forename: Jason
authors.initials: J
authors.lastname: Legg
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pujol
authors.forename: Ken
authors.initials: K
authors.lastname: Bridges
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000009:adverse effects; D001803:Blood Transfusion; D000068256:Darbepoetin alfa; D004311:Double-Blind Method; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage / Q000009:adverse effects*; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D012306:Risk; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D006397:Hematinics; D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa
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