Treating Anemia of Cancer with Every-4-Week Darbepoetin Alfa: Final Efficacy and Safety Results from a Phase II, Randomized, Double-Blind, Placebo-Controlled Study

Abstract

Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anemia. This phase II, double-blind, placebo-controlled study examined the efficacy of darbepoetin alfa for treating anemia of cancer (AoC) in patients not receiving chemotherapy or radiotherapy. Patients were randomized 3:1 to receive darbepoetin alfa (6.75 g/kg) or placebo every 4 weeks; the end of the study was at week 17. The primary endpoint was the percentage of patients with a hematopoietic response. Secondary endpoints included transfusion incidence and safety parameters. Efficacy analyses were performed on 162 patients in the darbepoetin alfa group and 56 patients in the placebo group. The Kaplan-Meier percentages of patients who achieved a hematopoietic response (darbepoetin alfa, 69%; placebo, 24%) or achieved the target hemoglobin (darbepoetin alfa, 85%; placebo, 50%) differed significantly between treatment groups. The transfusion incidence did not differ between treatment groups probably because of the low baseline transfusion rates in AoC patients. The incidence of adverse events (including on-study deaths) was similar in both groups. In conclusion, darbepoetin alfa appeared to be well tolerated and significantly increased hemoglobin levels in these AoC study patients. The Oncologist 2008;13: 715-724

Effects of erythropoiesis-stimulating agents on fatigue- and anaemia-related symptoms in cancer patients: systematic review and meta-analyses of published and unpublished data

“…Of the 58 eligible RCTs, we excluded 21 RTCs for the following reasons: QoL data were not reported because of premature closure of the trials (Machtay et al , 2007; Thomas et al , 2008; AGO-OVAR 2.7; CR002305); or data reporting was too incomplete to allow any analysis (Rose et al , 1994; Dammacco et al , 2001; Quirt et al , 2001; Thomas et al , 2002; INT-1; INT-3; Leyland-Jones et al , 2005; Goss et al , 2005; Aapro et al , 2008a; Suzuki et al , 2008; EPO-GER-20; Gupta et al , 2009; Ray-Coquard et al , 2009; Yoshizaki et al , 2010; Untch et al , 2011; CDR0000069148; Moebus et al , 2013) (Figure 1). Finally, we included 37 studies with 10 581 patients randomised (Abels, 1993; Case et al , 1993; Henry and Abels, 1994; Thatcher et al , 1999; Littlewood et al , 2001; Huddart et al , 2002; Kotasek et al , 2002, 2003; Osterborg et al , 2002; Vansteenkiste et al , 2002; Boogaerts et al , 2003; Hedenus et al , 2003; Iconomou et al , 2003; Milroy et al , 2003; P-174; Chang et al , 2005; Debus et al , 2005; Mystakidou et al , 2005; O'Shaughnessy et al , 2005; Savonije et al , 2005; Witzig et al , 2005; Wilkinson et al , 2006; Charu et al , 2007; Wright et al , 2007; Gordon et al , 2008; Krzakowski, 2008; Pirker et al , 2008; Smith et al , 2008; Strauss et al , 2008; Christodoulou et al , 2009; Hernandez et al , 2009; Hoskin et al , 2009; OBE/EPO-INT-03; Tsuboi et al , 2009; Winquist et al , 2009; Engert et al , 2010; Pronzato et al , 2010). …”

“…Critical review of clinical study documents by the academic community may help to improve the quality of reporting in these reports, which will only be possible with open access to these documents. Second, we identified another 16 trials (Kotasek et al , 2002, 2003; Thomas et al , 2002; Vansteenkiste et al , 2002; Boogaerts et al , 2003; Hedenus et al , 2003; Goss et al , 2005; Mystakidou et al , 2005; Witzig et al , 2005; Wilkinson et al , 2006; Aapro et al , 2008a; Gordon et al , 2008; Krzakowski, 2008; Pirker et al , 2008; Strauss et al , 2008; EPO-GER-20, 2009a) measuring FACT-An that did not or only incompletely report their FACT-An results and could therefore not be included in our analyses. Access to IPD may have permitted to include these studies in our analysis and it is possible that including these studies would change the results of our analyses.…”

Economic evaluation of erythropoiesis‐stimulating agents for anemia related to cancer

“…The risk of mortality during the short‐term, probability of blood transfusion, and starting and ending hemoglobin values were based on weighted summary characteristics of the control arms of studies included in the systematic review (Table 1). Long‐term annual mortality was estimated from 16 studies that assessed mortality beyond the short‐term treatment period (average follow‐up duration 90 weeks) 12‐26. The weekly starting dose and duration of treatment was based on the intervention arm of included studies to define traditional ESA use.…”

“…The weekly starting dose and duration of treatment was based on the intervention arm of included studies to define traditional ESA use. The cumulative dose of ESA was inconsistently reported, but as the mean weekly dose did not appear to differ from the weekly starting dose when both were reported,13, 16, 17, 26‐31 the weekly dose was assumed to be constant over the duration of administration.…”

“…The relative risk of mortality for all ESA during the ESA treatment period was determined from the clinical systematic review; 6 studies reported mortality in patients who survived the short‐term treatment period during an additional 63 weeks,12‐17 from which the relative risk of mortality during the subsequent year was calculated (Table 1). The difference in the number of units (U) that were transfused per subject between treatment arms was determined from a meta‐analysis of studies in the clinical review.…”