Efficacy and Safety of Every-2-Week Darbepoetin Alfa in Patients with Anemia of Cancer: A Controlled, Randomized, Open-Label Phase II Trial

Charu, Veena; Belani, Chandra P.; Gill, Ahmad N.; Bhatt, Mukesh; Tomita, Dianne; Rossi, G.; Ben-Jacob, A.

doi:10.1634/theoncologist.12-6-727

Cited by 26 publications

(4 citation statements)

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“…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). …”

Section: Resultsmentioning

confidence: 99%

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on fatigue- and anaemia-related symptoms in cancer patients: systematic review and meta-analyses of published and unpublished data

et al. 2014

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Background:Erythropoiesis-stimulating agents (ESAs) reduce the need for red blood cell transfusions; however, they increase the risk of thromboembolic events and mortality. The impact of ESAs on quality of life (QoL) is controversial and led to different recommendations of medical societies and authorities in the USA and Europe. We aimed to critically evaluate and quantify the effects of ESAs on QoL in cancer patients.Methods:We included data from randomised controlled trials (RCTs) on the effects of ESAs on QoL in cancer patients. Randomised controlled trials were identified by searching electronic data bases and other sources up to January 2011. To reduce publication and outcome reporting biases, we included unreported results from clinical study reports. We conducted meta-analyses on fatigue- and anaemia-related symptoms measured with the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and FACT-Anaemia (FACT-An) subscales (primary outcomes) or other validated instruments.Results:We identified 58 eligible RCTs. Clinical study reports were available for 27% (4 out of 15) of the investigator-initiated trials and 95% (41 out of 43) of the industry-initiated trials. We excluded 21 RTCs as we could not use their QoL data for meta-analyses, either because of incomplete reporting (17 RCTs) or because of premature closure of the trial (4 RCTs). We included 37 RCTs with 10 581 patients; 21 RCTs were placebo controlled. Chemotherapy was given in 27 of the 37 RCTs. The median baseline haemoglobin (Hb) level was 10.1 g dl–1; in 8 studies ESAs were stopped at Hb levels below 13 g dl–1 and in 27 above 13 g dl–1. For FACT-F, the mean difference (MD) was 2.41 (95% confidence interval (95% CI) 1.39–3.43; P<0.0001; 23 studies, n=6108) in all cancer patients and 2.81 (95% CI 1.73–3.90; P<0.0001; 19 RCTs, n=4697) in patients receiving chemotherapy, which was below the threshold (⩾3) for a clinically important difference (CID). Erythropoiesis-stimulating agents had a positive effect on anaemia-related symptoms (MD 4.09; 95% CI 2.37–5.80; P=0.001; 14 studies, n=2765) in all cancer patients and 4.50 (95% CI 2.55–6.45; P<0.0001; 11 RCTs, n=2436) in patients receiving chemotherapy, which was above the threshold (⩾4) for a CID. Of note, this effect persisted when we restricted the analysis to placebo-controlled RCTs in patients receiving chemotherapy. There was some evidence that the MDs for FACT-F were above the threshold for a CID in RCTs including cancer patients receiving chemotherapy with Hb levels below 12 g dl–1 at baseline and in RCTs stopping ESAs at Hb levels above 13 g dl–1. However, these findings for FACT-F were not confirmed when we restricted the analysis to placebo-controlled RCTs in patients receiving chemotherapy.Conclusions:In cancer patients, particularly those receiving chemotherapy, we found that ESAs provide a small but clinically important improvement in anaemia-related symptoms (FACT-An). For fatigue-related symptoms (FACT-F), the overall effect did not reach the threshold for a CID.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2014

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“…Previous studies have yielded conflicting results on the effectiveness of ESAs in reducing transfusion requirements in patients with AoC. For example, in three open-label studies, ESAs reduced transfusion requirements [15,16,21]; however, in three placebo-controlled trials, only trends toward a lower transfusion incidence in the ESA-treated group than in the placebo group were observed [14,17,22]. Likewise, in the present study, although darbepoetin alfa increased hemoglobin levels above those attained with placebo, there was no significant difference in the incidence of transfusions between the two treatment groups.…”

Section: Discussionmentioning

confidence: 99%

“…There are also conflicting data on the effect of ESAs on the quality of life of patients with AoC. In a number of studies, quality-of-life measures were improved after treatment with ESAs [15,17,21,25]; however, in a recently completed large, placebo-controlled study of darbepoetin alfa in patients with AoC, darbepoetin alfa did not improve FACT-F scores above those observed with placebo [26]. In the present study, both treatment groups had a clinically meaningful rise (three or more points) [27] in FACT-F score from baseline, but darbepoetin alfa did not improve FACT-F scores above those observed with placebo.…”

Section: Discussionmentioning

confidence: 99%

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

Gordon

Nichols

Ben-Jacob³

et al. 2008

The Oncologist

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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

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“…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.…”

Section: Methodsmentioning

confidence: 99%

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

Klarenbach¹,

Manns²,

Reiman³

et al. 2010

Cancer

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BACKGROUND:Erythropoiesis‐stimulating agents (ESA) administered to cancer patients with anemia reduce the need for blood transfusions and improve quality‐of‐life (QOL). Concerns about toxicity have led to more restrictive recommendations for ESA use; however, the incremental costs and benefits of such a strategy are unknown.METHODS:The authors created a decision model to examine the costs and consequences of ESA use in patients with anemia and cancer from the perspective of the Canadian public healthcare system. Model inputs were informed by a recent systematic review. Extensive sensitivity analyses and scenario analysis rigorously assessed QOL benefits and more conservative ESA administration practices (initial hemoglobin [Hb] <10 g/dL, target Hb ≤12 g/dL, and chemotherapy induced anemia only).RESULTS:Compared with supportive transfusions only, conventional ESA treatment was associated with an incremental cost per quality‐adjusted life year (QALY) gained of $267,000 during a 15‐week time frame. During a 1.3‐year time horizon, ESA was associated with higher costs and worse clinical outcomes. In scenarios where multiple assumptions regarding QOL all favored ESA, the lowest incremental cost per QALY gained was $126,000. Analyses simulating the use of ESA in accordance with recently issued guidelines resulted in incremental cost per QALY gained of >$100,000 or ESA being dominated (greater costs with lower benefit) in the majority of the scenarios, although greater variability in the cost‐utility ratio was present.CONCLUSIONS:Use of ESA for anemia related to cancer is associated with incremental cost‐effectiveness ratios that are not economically attractive, even when used in a conservative fashion recommended by current guidelines. Cancer 2010. © 2010 American Cancer Society.

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Efficacy and Safety of Every-2-Week Darbepoetin Alfa in Patients with Anemia of Cancer: A Controlled, Randomized, Open-Label Phase II Trial

Cited by 26 publications

References 26 publications

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

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

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

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

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