ALBERT

Description: Although pharmacokinetic differences between EPO and DARB are known, clinical comparisons are best determined through randomized clinical trials. This randomized, open-label, multicenter study was designed to compare the efficacy of EPO and DARB for the treatment of CT-induced anemia using dosing consistent with the 2004 NCCN Cancer and Treatment-Related Anemia Guidelines. Hb response, transfusions (TFNs), and safety were assessed in patients (pts): ≥18 y with solid tumors; with baseline (BL) Hb ≤11 g/dL; scheduled to receive CT for ≥12 wks; and no prior erythropoietin therapy within 3 months. Pts were stratified by CT type (platinum/nonplatinum) then randomized 1:1 to EPO 40,000 U SC QW or DARB 200 μg SC Q2W for up to 16 wks. Dose increases were required for nonresponders (13 g/dL, study drug was held and then reduced, and if Hb increased 〉1.3 g/dL (EPO) or 〉1.0 g/dL (DARB) in a 2-wk period, dose was reduced. Pts were withdrawn if CT was discontinued or CT type changed from platinum to nonplatinum or vice versa. Primary efficacy endpoint is Hb response rate (HRR; proportion of pts achieving an Hb increase of ≥1 g/dL from BL during the first 4 weeks) excluding Hb values within 28 days following a TFN. Primary analysis is a logistic regression model (treatment group and CT type as factors) comparing HRRs between the 2 treatment groups. A maximum of 400 pts could have been randomized; however, a prespecified IA of the primary endpoint using logistic regression was to be performed after the first 300 pts completed 4 wks of therapy. If the IA demonstrated that P≤.0125 (1-sided), then the treatment difference between EPO and DARB was considered statistically significant in favor of EPO and enrollment would be terminated. 339 pts (170 EPO, 169 DARB) comprised a modified intent-to-treat (MITT) population (pts with ≥1 dose of study drug and ≥1 postbaseline Hb or TFN value). 305 (151 EPO, 154 DARB) of these pts had completed 4 wks of therapy by the same date and were included in the IA. The IA demonstrated a statistically significantly higher HRR for EPO pts, 47%, compared with DARB pts, 33%, P=.0078 (1-sided). Enrollment was terminated; some patients remain on study. Demographics for all randomized patients were similar for EPO/DARB (mean age: 62/63 y; men: 38/31%; ECOG PS 0–1: 86/82%; and nonplatinum CT: 62/58%). Most common tumor types were breast, lung, and colorectal. In the MITT population, mean BL Hb was 10.1 g/dL in each group and Hb increases for EPO and DARB, respectively, were 0.7 and 0.3 g/dL after 4 wks, 1.0 and 0.5 g/dL after 8 wks, 1.3 and 0.7 g/dL after 12 wks, and 1.3 and 0.7 g/dL after 16 wks; last-value-carried-forward method used to impute missing Hb values and Hb values within 28 days following RBC TFN. After study day 28, 22/170 (13%) EPO pts and 28/169 (17%) DARB pts received RBC or whole blood TFN. Available data suggest a similar safety profile for the 2 agents. This study demonstrated that pts treated with EPO 40,000 U SC QW had a significantly greater HRR during the first 4 wks of therapy compared with DARB 200 μg SC Q2W. In addition, EPO-treated pts had greater Hb increases throughout the study compared with DARB.

Description: Epoetin alfa (EPO) 40,000–60,000 U SC once weekly (QW) has been shown to increase hemoglobin (Hb) by ~2 g/dL after 8-12 wks in anemic patients (pts) with cancer receiving chemotherapy (CT). The proportion of pts achieving a hematologic response (HR; Hb ≥12 g/dL and/or Hb increase ≥2 g/dL from baseline [BL]) at this dosage was ~70%. It was hypothesized that higher initiation doses of EPO may result in earlier HR and improved HR rates. This nonrandomized, open-label, pilot study was designed to investigate the safety and efficacy of EPO 80,000 U SC QW for up to 12 wks in anemic (Hb ≤11 g/dL) pts with nonmyeloid malignancies undergoing CT. If Hb increased to 〉13 g/dL, EPO was held until Hb ≤12 g/dL, then dose reduced by 20,000 U. Dose was similarly reduced if Hb increased 〉1.3 g/dL in 2 wks. Primary endpoint was proportion of pts with a major response, defined as HR. Secondary endpoints included proportion of pts with a minor response (Hb increase ≥1 g/dL but

Description: Patients (pts) with cancer often become anemic as a result of the disease and its treatment. Epoetin alfa (EPO) administered 150 U/kg SC 3 times a week in pts with cancer-related anemia not receiving chemotherapy (CT) or radiation therapy (RT) significantly reduces transfusion requirements, increases hemoglobin (Hb), and improves quality of life (QOL). EPO 40,000 U SC QW is effective in pts with cancer-related anemia receiving CT +/− RT and may be a treatment option for pts not receiving CT or RT. This open-label, multicenter, pilot study investigated clinical outcomes and safety of EPO 40,000 U SC QW in anemic (Hb 1.3 g/dL over 2 wks in the original protocol. Primary endpoint was proportion of pts achieving a ≥1-g/dL or ≥2-g/dL increase in Hb from baseline (BL; independent of transfusion within the previous 28 days) at any time during the study. Secondary endpoints included transfusion requirements and QOL (measured with the Linear Analog Scale Assessment; LASA). The study was temporarily suspended due to concerns of a potential increased risk of thrombotic events if Hb 〉13 g/dL, and restarted with an upper Hb limit of 13 g/dL and rate of rise of Hb of 1 g/dL over any consecutive 2-wk period, independent of transfusion. Due to the interruption in therapy, 3 efficacy populations were evaluated: pts who had a post BL Hb value or transfusion (modified intent-to-treat [MITT], n=91); pts who completed the study prior to suspension (presuspension, n=37); and pts who entered the study, had treatment suspended, and completed after the study was restarted (suspension, n=33). Ninety-five pts were evaluable for safety: mean age, 69 years; 45% women; 85% ECOG 0-1; mean BL Hb 10.4 ± 0.73 g/dL. For the 3 populations analyzed, 73/91 (80%), 33/37 (89%), and 29/33 (88%) pts had an Hb increase ≥2 g/dL for the MITT, presuspension, and suspension populations, respectively. 13/91 (14%), 2/37 (5%), and 3/33 (9%) pts had at best an Hb increase ≥1 g/dL for the MITT, presuspension, and suspension populations, respectively. For the MITT population, mean change in Hb from BL after 12 wks was 2.9 ± 1.54 g/dL. Mean Hb decreased 1.4 ± 1.10 g/dL during the posttreatment observation period. One pt was transfused on study. Both wk 9 and wk 17 LASA scores increased significantly from BL in all categories (Energy Level, Daily Activities, and Overall QOL; P

Description: Background: Various metrics have been used to evaluate the efficacy of erythropoietic agents for the treatment of chemotherapy-related anemia (CRA) including the proportion of patients attaining a ≥1 or ≥2g/dL increase in hemoglobin (Hb), Hb change from baseline at weeks 4, 8, 12 and 16, area under the change in Hb curve (Hb AUC) and the proportion of patients achieving a target Hb level. Many trial protocols and national treatment guidelines recommend dose escalation of these agents after the first 4 or 6 weeks of treatment if the patient fails to obtain a ≥1g/dL rise in Hb. Studies have also shown that an early Hb response is associated with improved clinical outcomes, i.e. lower transfusion requirements and greater gains in quality of life; but, it is not known how well early Hb response correlates with alternative efficacy metrics. Objective: To compare several alternative measures of treatment efficacy between patients who attained an early Hb response to those who did not while receiving an erythropoietic agent for treatment of CRA. Methods: Using preliminary data from an ongoing randomized, multi-center, 16-week, open-label trial of epoetin alfa versus darbepoetin alfa, we dichotomized patients based on early Hb response (≥1 g/dL Hb rise during the first 4 weeks of treatment) and calculated several alternative measures of efficacy. Only observed, patient-level data were analyzed in the base-case analyses. Sensitivity analyses were performed to evaluate the impact of employing various methods to handle missing data, excluding Hb values within 28 days following a transfusion, limiting analyses to patients with ≥8 or 12 weeks of follow-up, and limiting analyses to Hb values obtained after 4 weeks of treatment. Comparisons were performed using chi-square and Wilcoxon rank-sum tests for categorical and continuous metrics, respectively. Results: 274 patients were analyzed; 134 had an early Hb response, 140 did not. The mean duration of follow-up was 10.1 weeks. All metrics indicated superior longer-term response among patients who had an early Hb response compared to those who did not. These findings were robust across sensitivity analyses. Comparisons of Patients Achieving and Not Achieving Early Hemoglobin Response Comparisons of Patients Achieving and Not Achieving Early Hemoglobin Response Metric Early Response (n=134) No Early Response (n=140) p-value Mean Hb at baseline 10.05 g/dL 10.18 g/dL 0.7178 Mean Hb at 4 weeks 11.58 g/dL 9.89 g/dL

Description: Epoetin alfa (EPO) 40,000–60,000 U administered SC QW has been shown to significantly reduce transfusion utilization, increase Hb, and improve quality of life in anemic patients (pts) with cancer receiving chemotherapy (CT). The use of higher initiation doses of epoetin alfa followed by less frequent maintenance dosing was evaluated to provide convenience and dosing flexibility for both pts and clinicians. This open-label, multicenter, pilot study investigated the efficacy of EPO at a starting dose of 60,000 U SC QW for 4 weeks (wks) followed by 60,000 U SC administered every 2 weeks (Q2W) for up to 12 wks in anemic (Hb1.3 g/dL in 2 wks, EPO was held until Hb was 1 g/dL) to this initial dosing regimen, which compares favorably with responses seen with a lower starting dose (40,000 U SC QW with dose escalation to 60,000 U SC QW). In addition, pts were able to maintain or extend this response with a 60,000 U SC Q2W dosing regimen thereafter.

Description: 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

Description: Epoetin alfa has been shown to increase hemoglobin (Hb), decrease transfusion requirements, and improve quality of life (QOL) in patients receiving chemotherapy (CT) and/or radiotherapy (RT). However, the efficacy of epoetin alfa in cancer patients receiving neither CT nor RT is not as well characterized, particularly at doses less frequent than 3 times weekly. The objective of this open-label, nonrandomized, multicenter pilot study was to evaluate epoetin alfa 60,000 U subcutaneously (SC) every 2 weeks (Q2W) in 50 anemic patients with cancer who were not receiving CT or RT. The primary efficacy endpoint is the proportion of patients achieving a hematopoietic response (HR; Hb increase ≥2 g/dL from baseline and/or Hb increase to ≥12 g/dL at any scheduled visit) independent of transfusion within 28 days. Patients with histologically confirmed nonmyeloid malignancy, Hb ≤11 g/dL, and who had not received CT in the previous 8 weeks or RT in the previous 4 weeks were enrolled. Patients were permitted to receive hormonal therapy, androgen deprivation therapy, and/or immunotherapy. Patients were to receive epoetin alfa 60,000 U SC Q2W, with escalation to 80,000 U Q2W after 4 weeks if Hb increased ≤1 g/dL. Dose will be titrated to maintain Hb ≤13 g/dL; all patients were to receive oral ferrous sulfate 325 mg daily. Patients will be treated for up to 12 weeks, with a 4-week follow-up after last dose of study drug. As of July 2004, 18 patients are evaluable for efficacy (modified intent-to-treat, ie, all enrolled patients who received ≥1 dose of study drug and had ≥1 postbaseline Hb or transfusion evaluation) and 18 for safety (all enrolled patients who received ≥1 dose of study drug). Mean age was 74.4 ± 8.7 yrs, mean baseline Hb was 10.0 ± 1.0 g/dL (n=18), and 7/18 were men. Of these patients, 7 completed 4 weeks, 3 completed 8 weeks, and 1 completed 12 weeks on study. The HR of these patients was assessed regardless of how many weeks of study they completed at the time of this interim analysis; HR was 44.4%. Hb increased 1.4 ± 0.7 g/dL (n=11) after 4 weeks and 1.2 ± 1.4 g/dL (n=4) after 8 weeks of treatment. Adverse events were limited to 1 patient, who experienced back pain and epistaxis. No patients died during the study, and no thrombotic vascular events were reported. Early results of this study suggest that epoetin alfa 60,000-80,000 U SC given every other week is well tolerated and appears to effectively increase Hb in anemic cancer patients not receiving CT or RT. The study is currently ongoing.