Comparison of the therapeutic effects of epoetin zeta to epoetin alfa in the maintenance phase of renal anaemia treatment

Abstract The efficacy of epoetin alfa (EPO) 40,000 U SC once weekly (QW) has been established in clinical studies in anemic patients (pts) with cancer receiving chemotherapy (CT). Higher starting doses of EPO may increase initial hemoglobin (Hb) response and subsequent less frequent maintenance dosing may improve dosing flexibility for pts and health care providers. This ongoing, open-label, multicenter, 24-week (wk) study was designed to evaluate the efficacy and safety of EPO at a starting dose of 60,000 U SC QW to a target Hb of 12 g/dL in the Initiation Phase (IP; maximum of 12 wks), followed by 80,000 U SC every 3 wks (Q3W) in the Maintenance Phase (MP) to maintain Hb in the range 11.5–12.5 g/dL. Eligible pts were ≥18 years with nonmyeloid malignancy, had baseline (BL) Hb <11 g/dL, and were scheduled to receive CT Q3W for ≥15 wks. Pts who achieved Hb ≥12 g/dL during the IP subsequently entered the MP; however, pts did not receive the first Q3W maintenance dose until start of the next Q3W CT cycle. Pts were withdrawn if Hb decreased to <11 g/dL during the MP. The primary endpoint was proportion of pts in the IP who achieved an Hb ≥12 g/dL or an Hb increase ≥2 g/dL from BL. Secondary endpoints included Hb increase ≥1 g/dL but <2.0 g/dL from BL in IP, maintenance of mean Hb 11.5–12.5 g/dL in the MP, maintenance of mean Hb >11.0 g/dL but <11.5 g/dL in MP, Hb over time, and transfusions. All Hb and response rates were independent of RBC transfusion within the previous 28 days. Study enrollment was terminated at 115 pts. In this preliminary analysis, the first 69 pts (mean age, 62 years; 65% women; 87% ECOG 0-1) enrolled and who received ≥1 dose of study drug were evaluable for safety and efficacy. Mean BL Hb was 10.2 ± 0.8 g/dL. The proportion of pts in the IP who achieved an Hb ≥12 g/dL or an Hb increase ≥2 g/dL from BL was 74% (49/69). The proportion of pts in the IP with an Hb increase ≥1 g/dL but <2 g/dL from BL was 9% (6/69). Forty-one (59%) pts entered the MP after a median of 5.0 wks in the IP and spent an average of 7.1 wks in the MP. Of these pts, 33 (80%) maintained an average Hb of 11.5–12.5 g/dL and 3 (7%) maintained an average Hb >11.0 g/dL but <11.5 g/dL over the course of the MP. During the MP, mean Hb was 12.1 ± 0.6 g/dL at entry, 11.8 ± 1.0 g/dL (n=15) after 8 wks of Q3W dosing, and 11.6 ± 1.1 g/dL (n=38) at final value. Eleven (27%) pts were withdrawn during the MP because Hb decreased to <11 g/dL. EPO dose was reduced in 25% (17/69) of pts in the IP and in 39% (16/41) of pts in the MP due to Hb >13 g/dL or Hb increase >1.3-g/dL in 2 wks. Thirty-five percent (24/69) of pts had a dose of EPO held at any time during the study for Hb >13 g/dL or another reason. Five (7%) pts were transfused after study day 28. Twenty-six (38%) pts experienced serious adverse events (AEs). Eight (12%) pts experienced a clinically relevant thrombovascular event. Two (3%) pts discontinued due to AEs. Nine (13%) pts died during the study or within the 90-day follow-up period. These preliminary data suggest that initial dosing of EPO 60,000 U QW is associated with a hematopoietic response rate (Hb ≥12 g/dL or Hb increase ≥2 g/dL from BL) of ~75% in pts with cancer and anemia receiving CT, similar to the response rate reported historically for EPO 40,000 U SC QW with dose escalation to 60,000 U SC QW. In addition, among pts who achieved a target Hb ≥12 g/dL with QW dosing and then received Q3W maintenance dosing, EPO 80,000 U SC Q3W maintained mean Hb above 11 g/dL in >85% of pts.

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Epoetin alfa helps improve QOL in renal anaemia

PharmacoEconomics & Outcomes News ◽

10.1007/bf03275884 ◽

2003 ◽

Vol 400 (1) ◽

pp. 10-10

Keyword(s):

Epoetin Alfa ◽

Renal Anaemia

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Epoetin biosimilars in the management of anemia secondary to chemotherapy in patients with solid tumors, lymphomas, and myelomas: The ORHEO study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.9564 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 9564-9564

Author(s):

Elisabeth Luporsi-Gely ◽

Pierre-Louis Soubeyran ◽

Mauricette Michallet

Keyword(s):

Adverse Events ◽

Solid Tumors ◽

Patient Characteristics ◽

Epoetin Alfa ◽

Related Data ◽

Epoetin Zeta ◽

Post Marketing ◽

Almost All ◽

Rate Of Response ◽

Clinical Trial Information

9564 Background: Chemotherapy may induce anemia with potentially severe consequences. The ORHEO (place of biOsimilaRs in the therapeutic management of anaemia secondary to chemotherapy in HaEmatology and Oncology) study examined the efficacy and safety of epoetin alfa biosimilars (EABs) for the treatment of chemotherapy-induced anemia (CIA) in the clinical setting. Methods: ORHEO was a multicenter, observational, prospective, post-marketing study conducted in France. Patients with CIA (Hb <110g/L) >18 years old, with solid tumors, lymphomas or myelomas and eligible for epoetin alfa treatment were included in the study; they received EAB as prescribed by their physician. Baseline patient characteristics and anemia-related data including baseline and target Hb level epoetin treatment, adverse events and any other concomitant treatments prescribed were recorded. The primary endpoint was the rate of responders (defined as an increase in Hb levels to 100 g/L or at least 10 g/L since inclusion visit, or reaching target Hb set at start of study, without any blood transfusions in the 3 weeks prior to measurement) at +3 months (M3). Other endpoints included rate of responders at +6 months (M6) and safety endpoints. Results: 2310 patients (51.43 % male, 48.57 % female) from 232 centers were included in this study. At baseline 79.6% had solid tumors, 13.0% lymphomas and 7.4% myelomas. Median age was 68 y (range: 18–93). Mean baseline Hb level was 96 g/L with a target Hb level of >= 120 g/L for 52.7% of patients. Almost all (99.9%) received the biosimilar epoetin zeta (median dose 30,000 IU/week) with 26.6% receiving additional iron supplementation. A total of 2056 and 1664 patients had at least one Hb level value at M3 and M6 respectively. The rate of response was 81.6% and 86.5% at M3 and M6, respectively. In total, 17.0% of treated patients reported clinically relevant adverse events (all grades), the most common being infections (5.0%) and thromboembolic events (3.5%). Transfusion rates were reported as 9.4% and 5.8% at M3 and M6, respectively. No EAB-related deaths were reported. Conclusions: EAB was effective and well-tolerated in the management of CIA. Clinical trial information: NCT01626547.

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Maintenance Dosing with Epoetin alfa Every Three Weeks (Q3W) in Anemic Patients with Cancer Receiving Chemotherapy Every Three Weeks: Final Results.

Blood ◽

10.1182/blood.v106.11.3555.3555 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3555-3555 ◽

Cited By ~ 5

Author(s):

Vernon P. Montoya ◽

John Xie ◽

Richard C. Woodman

Keyword(s):

Adverse Events ◽

Maintenance Therapy ◽

Maintenance Phase ◽

Epoetin Alfa ◽

Open Label ◽

Vascular Events ◽

Serious Adverse Events ◽

Initiation Phase ◽

Multi Center Study ◽

Hematopoietic Response

Abstract Although epoetin alfa is commonly used weekly for the treatment of chemotherapy (CT)-induced anemia, most CT is given at three week intervals. Therefore, to provide increased patient convenience we examined a dosing regimen that would allow patients to receive epoetin alfa 80,000 U Q3W during maintenance therapy. This open-label, multi-center study had two phases: Initiation Phase (IP) of 60,000 U QW to achieve target hemoglobin (Hb) of 12 g/dL (maximum duration 12 weeks), followed by a Maintenance Phase (MP) of 80,000 U Q3W to maintain Hb between 11.0 and 12.5 g/dL. Only those patients achieving Hb ≥ 12 g/dL in the IP entered the MP; once target Hb was achieved, patients proceeded to MP at the beginning of their next full CT cycle. Patients were withdrawn from the MP if Hb decreased to < 11 g/dL. Doses were held for Hb > 13 g/dL and reduced for rate of rise > 1.3 g/dL/2 weeks. Maximum study duration (IP + MP) was 24 weeks. Patients ≥ 18 years of age with non-myeloid malignancy, baseline Hb ≤ 11 g/dL, and CT planned Q3W for ≥ 15 weeks were enrolled. Endpoints included proportion of patients achieving hematopoietic response in the IP (≥ 2 g/dL Hb increase from baseline or Hb ≥ 12 g/dL) and proportion maintaining mean Hb between 11.0 and 12.5 g/dL in the MP. Also analyzed was the proportion of patients maintaining mean Hb between 11.0 and 13.0 g/dL in the MP. A total of 115 patients were enrolled and received at least one dose of epoetin alfa; mean age was 62.2 ± 11.9 years, 66.1% were female, mean baseline Hb was 10.2 ± 0.8 g/dL, and 86.1% had solid tumors. During the IP, 84 of 115 (73.0%) patients achieved hematopoietic response (≥ 2 g/dL Hb increase from baseline or Hb ≥ 12 g/dL). Seventy-three patients (63.5%) who achieved Hb ≥ 12 g/dL entered the MP after a median of 6.0 weeks in IP and spent a mean of 9.8 weeks in MP. Fifty-four of 73 (74.0%) maintained an average Hb between 11.0 and 12.5 g/dL over the course of the MP; 64 (87.7%) maintained an average Hb between 11.0 and 13.0 g/dL over the course of the MP. Twenty-five (34.2%) patients were withdrawn from the MP because Hb decreased to < 11 g/dL. Of 115 patients dosed in IP, 30 (26.1%) had doses reduced and 31 (27.0%) had doses held; of 73 patients dosed in MP, 9 (7.8%) had doses reduced and 16 (13.9%) had doses held. Fifty-one (44.3%) patients experienced serious adverse events. Eleven (9.6%) patients experienced clinically relevant thrombotic vascular events. Two and 4 patients discontinued due to adverse events in the IP and MP, respectively. Eight (7.0%) patients died during the study or within 30 days after last study dose. Although 60,000 U QW was used during the IP to achieve a HR, 40,000 U QW is the recommended initiation dose of epoetin alfa. This study suggests that epoetin alfa 80,000 U administered every three weeks to patients on a Q3W CT regimen is an effective option for maintenance therapy of CT-induced anemia.

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Phase III Study of Two Different Dosing Schedules of Erythropoietin in Anemic Patients With Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.7276 ◽

2006 ◽

Vol 24 (7) ◽

pp. 1079-1089 ◽

Cited By ~ 37

Author(s):

David P. Steensma ◽

Roy Molina ◽

Jeff A. Sloan ◽

Daniel A. Nikcevich ◽

Paul L. Schaefer ◽

...

Keyword(s):

Maintenance Phase ◽

Drug Dose ◽

Phase Iii ◽

Epoetin Alfa ◽

Patients With Cancer ◽

Global Quality ◽

Global Quality Of Life ◽

Phase Iii Study ◽

To Receive

PurposeTo compare maintenance epoetin alfa administered once every 3 weeks with continued weekly epoetin alfa for patients with cancer-associated anemia.Patients and MethodsEligible patients were randomly assigned at enrollment to receive three weekly doses of epoetin alfa 40,000 U subcutaneously (SC), followed by either standard weekly epoetin alfa (40K arm) or 120,000 U of epoetin alfa (120K arm) SC every 3 weeks for 18 additional weeks.ResultsThree hundred sixty-five patients were enrolled. One hundred eighty-three patients were assigned to the 40K arm, and 182 were assigned to the 120K arm. There was no difference in the proportion of patients requiring transfusions during the study (23% in 40K arm and 18% in 120K arm, P = .22) or specifically during the maintenance phase (13% in 40K arm v 15% in 120K arm, P = .58). Patients randomly assigned to the 40K arm were more likely to have a ≥ 2 or ≥ 3 g/dL hemoglobin (Hb) increment, were more likely to have a drug dose held because of high Hb, and had higher mean end-of-study Hb levels. Toxicities, including thromboembolism, and overall survival were similar. Patients in the 40K arm had a higher global quality of life (QOL) at baseline for unclear reasons, whereas patients in the 120K arm had a greater global QOL improvement during the study, so end-of-study QOL was equivalent.ConclusionAfter three weekly doses of epoetin alfa 40,000 U, a dose of 120,000 U can be administered safely once every 3 weeks without increasing transfusion needs or sacrificing QOL. The Hb increment is somewhat greater with continued weekly epoetin alfa. Lack of blinding as a result of different treatment schedules may have confounded results.

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Switching epoetin alfa and epoetin zeta in patients with Renal Anemia on Dialysis: Posthoc analysis

Advances in Therapy ◽

10.1007/s12325-010-0080-z ◽

2010 ◽

Vol 27 (12) ◽

pp. 941-952 ◽

Cited By ~ 26

Author(s):

Andrzej Więcek ◽

Islah Ahmed ◽

Paul Scigalla ◽

Rossen Koytchev

Keyword(s):

Renal Anemia ◽

Epoetin Alfa ◽

Epoetin Zeta

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Effects and Safety of a Novel Oral Potassium-Lowering Drug-Sodium Zirconium Cyclosilicate for the Treatment of Hyperkalemia: a Systematic Review and Meta-Analysis

Cardiovascular Drugs and Therapy ◽

10.1007/s10557-020-07134-2 ◽

2021 ◽

Author(s):

Yaru Zhang ◽

Ruiling Xu ◽

Fanghao Wang ◽

Youxia Liu ◽

Junying Xu ◽

...

Keyword(s):

Serum Potassium ◽

Meta Analysis ◽

Statistical Significance ◽

Maintenance Phase ◽

Cochrane Library ◽

Therapeutic Effects ◽

Rapid Reduction ◽

Sodium Zirconium ◽

Sodium Zirconium Cyclosilicate

Abstract Background Oral sodium zirconium cyclosilicate (SZC) is a novel potassium binder capable of achieving a rapid reduction of serum potassium (sK+) and maintaining a long-term normokalemia. We undertook a meta-analysis to summarize and evaluate the effects surrounding SZC in patients with hyperkalemia. Method We searched data sources from MEDLINE (from 1950 to Sep 2020), EMBASE (from 1970 to Sep 2020), and the Cochrane Library database (from 1950 to Sep 2020) for eligible studies. All randomized controlled trials (RCTs) regarding comparison of therapeutic effects of SZC in hyperkalemia participants were included. Results Seven studies, including 1697 patients with hyperkalemia, were analyzed. SZC significantly reduced mean sK+ (−0.42 mmol/L; 95% CI: −0.63 to −0.20 mmol/L, p = 0.0001) compared with placebo, with a significantly greater proportion of patients with normokalemia (RR 3.48, 95% CI 1.49 to 8.11, p = 0.004). Subgroup analyses showed that the longer durations of SZC treatment, the greater magnitudes of potassium reduction when compared with those of placebo (p between subgroups = 0.01) at correction phase. Besides, it also demonstrated sK+ tended to decrease more in patients who got longer treatment or larger dosage of SZC at maintenance phase; however, the difference did not reach statistical significance. Additionally, the drug was equally effective in studies with larger than 50% of patients with chronic kidney disease (CKD) or diabetes or patients using renin-angiotensin aldosterone system inhibitor (RAAS) inhibitors (all p < 0.05). The risk of edema (4.30, 1.17 to 15.84; p = 0.03) in SZC group was higher than those of placebo group. No statistically significant differences in the risks of other adverse events were observed between the two groups. Conclusions SZC effectively decreased the sK+ level in patients with hyperkalemia within 48 h and had benefits in the long-term control of serum potassium in patients who continued to receive SZC with a favorable safety profile from available data.

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