No support for darbepoetin-α in anaemia of cancer

Inpharma 1627 - 1 Mar 2008 No support for darbepoetin-α in anaemia of cancer In the wake of the Amgen 103 trial, there is heightened concern regarding the safety of erythropoiesis-stimulating agents (ESAs). The results of the Amgen study suggest that whether or not an anaemic patient is receiving myelosuppressive chemotherapy is a "clinically relevant distinction with therapeutic implications", according to David Steensma from the Mayo Clinic in Rochester, Minnesota. 1 He believes that unless new data emerge, "we can’t afford to risk testing ESAs in this population again". The Amgen 103 trial randomly assigned 989 cancer patients with anaemia * to receive either SC darbepoetin- α 6.75 µg/kg every 4 weeks (n = 517) or placebo; these patients were not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy. 2 Those patients who completed 16 weeks’ treatment could continue their assigned therapy for a further 16 weeks. There was no significant difference in all occurrences of blood transfusions between weeks 5 and 17 for the two groups. The incidence of cardiovascular and thromboembolic events was increased among darbepoetin-α recipients versus controls (9.7% vs 7.7%), as was the incidence of serious and fatal adverse events (47.6% vs 40.9%. Significantly more darbepoetin-α recipients died during treatment or long-term follow-up, compared with placebo recipients, with an estimated median time to death of 37 weeks versus 47 weeks, respectively. Long-term survival data favoured placebo recipients (hazard ratio 1.22; 95% CI 1.03, 1.45). The higher proportion of deaths among darbepoetin-α recipients "was unexpected", according to the study authors. * haemoglobin (Hb) ≤ 11 g/dL 1. Steensma DP. Is anemia of cancer different from chemotherapy-induced anemia? Journal of Clinical Oncology 26: 1022-1024, No. 7, 1 Mar 2008. 2. Smith Jr RE, et al. Darbepoetin alfa for the treatment of anemia in patients with active cancer not receiving chemotherapy or radiotherapy: results of a phase III, multicenter, randomized, double-blind, placebo-controlled study. Journal of Clinical Oncology 26: 1040-1050, 1 Mar 2008. 801099467 » Editorial comment: In March 2007, the US FDA issued a Public Health Advisory about serious life-threatening adverse effects associated with the use of the recombinant erythropoietins darbepoetin-α [Aranesp] and epoetin-α [Epogen and Procrit]. Product labelling was amended to include updated warnings, a new boxed warning and modifications to the dosing instructions [see Inpharma 1579 p22; 801013918]. In April, Health Canada recommended similar labelling changes [see Inpharma 1585 p20; 801069309]. Similarly, the EMEA reviewed the safety of ESAs, concluding that their benefits continue to outweigh the risks in approved indications, and recommended changes to product labelling. 1 Inpharma 1 Mar 2008 No. 1627 1173-8324/10/1627-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

date post
09-Dec-2016
Category

Documents
view
213
download
1

Embed Size (px):

Transcript of No support for darbepoetin-α in anaemia of cancer

Inpharma 1627 - 1 Mar 2008

No support for darbepoetin-αin anaemia of cancer

In the wake of the Amgen 103 trial, there isheightened concern regarding the safety oferythropoiesis-stimulating agents (ESAs). The results ofthe Amgen study suggest that whether or not ananaemic patient is receiving myelosuppressivechemotherapy is a "clinically relevant distinction withtherapeutic implications", according to David Steensmafrom the Mayo Clinic in Rochester, Minnesota.1 Hebelieves that unless new data emerge, "we can’t afford torisk testing ESAs in this population again".

The Amgen 103 trial randomly assigned 989 cancerpatients with anaemia* to receive either SC darbepoetin-α 6.75 µg/kg every 4 weeks (n = 517) or placebo; thesepatients were not receiving or planning to receivecytotoxic chemotherapy or myelosuppressiveradiotherapy.2 Those patients who completed 16 weeks’treatment could continue their assigned therapy for afurther 16 weeks. There was no significant difference inall occurrences of blood transfusions betweenweeks 5 and 17 for the two groups. The incidence ofcardiovascular and thromboembolic events wasincreased among darbepoetin-α recipients versuscontrols (9.7% vs 7.7%), as was the incidence of seriousand fatal adverse events (47.6% vs 40.9%. Significantlymore darbepoetin-α recipients died during treatment orlong-term follow-up, compared with placebo recipients,with an estimated median time to death of 37 weeksversus 47 weeks, respectively. Long-term survival datafavoured placebo recipients (hazard ratio 1.22; 95% CI1.03, 1.45). The higher proportion of deaths amongdarbepoetin-α recipients "was unexpected", accordingto the study authors.* haemoglobin (Hb) ≤ 11 g/dL

1. Steensma DP. Is anemia of cancer different from chemotherapy-inducedanemia? Journal of Clinical Oncology 26: 1022-1024, No. 7, 1 Mar 2008.

2. Smith Jr RE, et al. Darbepoetin alfa for the treatment of anemia in patients withactive cancer not receiving chemotherapy or radiotherapy: results of a phase III,multicenter, randomized, double-blind, placebo-controlled study. Journal ofClinical Oncology 26: 1040-1050, 1 Mar 2008.

801099467

» Editorial comment: In March 2007, the US FDA issued aPublic Health Advisory about serious life-threatening adverseeffects associated with the use of the recombinanterythropoietins darbepoetin-α [Aranesp] and epoetin-α [Epogenand Procrit]. Product labelling was amended to include updatedwarnings, a new boxed warning and modifications to the dosinginstructions [see Inpharma 1579 p22; 801013918]. In April,Health Canada recommended similar labelling changes [seeInpharma 1585 p20; 801069309]. Similarly, the EMEA reviewedthe safety of ESAs, concluding that their benefits continue tooutweigh the risks in approved indications, and recommendedchanges to product labelling.