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Purpose The Breast Cancer—Anemia and the Value of Erythropoietin (BRAVE) study evaluated whether epoetin beta would improve survival in patients with metastatic breast cancer (MBC). Patients and Methods BRAVE was an open-label, randomized, multicenter study in patients with MBC treated with anthracycline- and/or taxane-based chemotherapy. Patients (hemoglobin [Hb] < 12.9 g/dL) were randomly assigned (1:1) to epoetin beta 30,000 U subcutaneously once weekly or control for 24 weeks. The primary efficacy variable was overall survival. Secondary efficacy outcomes included progression-free survival, transfusion- and severe anemia–free survival, Hb response, safety, and quality of life (QoL). Results After 18 months of follow-up, 62 (27%) of 231 patients survived with epoetin beta therapy and 63 (27%) of 232 with control. No difference was detected in overall survival (hazard ratio [HR] = 1.07; 95% CI, 0.87 to 1.33, P = .522) or progression-free survival (HR = 1.07; 95% CI, 0.89 to 1.30, P = .448). There was a statistically significant benefit on transfusion- and severe anemia–free survival compared with control (HR = 0.59; P = .0097). Median Hb level increased with epoetin beta (11.7 g/dL at baseline to 13.3 g/dL at 24 weeks) but did not change with control (11.5 v 11.4 g/dL). Patients receiving epoetin beta experienced more thromboembolic events (TEEs) compared with controls (13% v 6%; P = .012) with no difference in serious TEEs (4% v 3%). Epoetin beta did not significantly improve QoL in this study where patients had a high baseline Hb value. Conclusion In patients with MBC receiving chemotherapy and initial Hb less than 12.9 g/dL, epoetin beta increased Hb. No difference was detected in overall survival. Because of its superiority design, this study cannot, however, exclude clinically important differences in survival with absolute certainty.

PURPOSE: To prospectively evaluate the effectiveness, safety, and clinical benefits of once-weekly epoetin alfa therapy as an adjunct to chemotherapy in anemic cancer patients. PATIENTS AND METHODS: A total of 3,012 patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this multicenter, open-label, nonrandomized study conducted in 600 United States community-based practices. Patients received epoetin alfa 40,000 U once weekly, which could be increased to 60,000 U once weekly after 4 weeks dependent on hemoglobin response. Treatment was continued for a maximum of 16 weeks. RESULTS: Among the 2,964 patients assessable for efficacy, epoetin alfa therapy resulted in significant increases in hemoglobin levels, decreases in transfusion requirements, and improvements in functional status and fatigue as assessed by the linear analog scale assessment (energy level, ability to perform daily activities, and overall quality of life) and the anemia subscale of the Functional Assessment of Cancer Therapy–Anemia questionnaire. Improvements in quality-of-life parameters correlated significantly (P < .001) with increased hemoglobin levels. The direct relationship between hemoglobin and quality-of-life improvement was sustained during the 16-week study period, which is similar to findings of large community-based trials of three-times-weekly dosing. Once-weekly epoetin alfa was well tolerated, with most adverse events attributed to the underlying disease or concomitant chemotherapy. CONCLUSION: The results from this large, prospective, community-based trial suggest that once-weekly epoetin alfa therapy increases hemoglobin levels, decreases transfusion requirements, and improves quality of life in patients with cancer and anemia who undergo concomitant chemotherapy. Based on the results of this study, the clinical benefits and the adverse event profile of once-weekly epoetin alfa therapy in community-based practice are similar to those observed in the historical experience with the three-times-weekly dosage schedule.

PURPOSE: This randomized, double-blind, placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements, hematopoietic parameters, quality of life (QOL), and safety in anemic cancer patients receiving nonplatinum chemotherapy. The study also explored a possible relationship between increased hemoglobin and survival. PATIENTS AND METHODS: Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels ≤ 10.5 g/dL, or greater than 10.5 g/dL but ≤ 12.0 g/dL after a hemoglobin decrease of ≥ 1.5 g/dL per cycle since starting chemotherapy, were randomized 2:1 to epoetin alfa 150 to 300 IU/kg (n = 251) or placebo (n = 124) three times per week subcutaneously for 12 to 24 weeks. The primary end point was proportion of patients transfused; secondary end points were change in hemoglobin and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study. RESULTS: Epoetin alfa, compared with placebo, significantly decreased transfusion requirements (P = .0057) and increased hemoglobin (P < .001). Improvement of all primary cancer- and anemia-specific QOL domains, including energy level, ability to do daily activities, and fatigue, was significantly (P < .01) greater for epoetin alfa versus placebo patients. Although the study was not powered for survival as an end point, Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa (P = .13, log-rank test), and Cox regression analysis showed an estimated hazards ratio of 1.309 (P = .052) favoring epoetin alfa. Adverse events were comparable between groups. CONCLUSION: Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy. Encouraging results regarding increased survival warrant another trial designed to confirm these findings.

PURPOSE To evaluate prospectively the effectiveness of epoetin alfa as an adjunct to chemotherapy in patients with cancer based on changes in quality-of-life parameters and hemoglobin levels, and to correlate these changes with antitumor response. PATIENTS AND METHODS Two thousand three hundred seventy patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this study from 621 US community-based practices. Patients received epoetin alfa 10,000 U three times weekly, which could be increased to 20,000 U three times weekly depending on the hemoglobin response at 4 weeks. Treatment continued for a maximum of 16 weeks in patients who showed evidence of hematologic response. RESULTS Two thousand two hundred eighty-nine patients (97%) were eligible for efficacy analyses. Epoetin alfa therapy was associated with improved quality-of-life parameters; these improvements correlated significantly with hemoglobin levels and were independent of tumor response. Provider-reported Karnofsky performance scores did not correlate with the improved quality-of-life changes. Epoetin alfa therapy was also associated with a significant increase in hemoglobin levels and decrease in transfusion use. Tumor type, chemotherapy agent/regimen, prior chemotherapy, baseline hemoglobin level, and baseline erythropoietin level were not predictive of a positive response to treatment. Epoetin alfa was well tolerated. CONCLUSION Epoetin alfa appears to have a beneficial impact on patient-reported functional capacity and quality of life in patients with cancer who received chemotherapy independent of tumor response. Concordantly, epoetin alfa appeared to increase hemoglobin levels and decrease transfusion use. Patients responded across all tumor types. The results suggest that epoetin alfa effectively improves functional outcomes in patients with cancer who receive chemotherapy.

e20616 Background: New data are available from two trials of ESA use in patients with breast cancer receiving chemotherapy. We conducted a meta-analysis of trials of ESA use in this population. Methods: A literature search identified reports from 1997-2012 that included mortality data from controlled ESA trials (epoetin alfa, epoetin beta, darbepoetin alfa, biosimilars) in patients with breast cancer receiving chemotherapy. We used data from company databases for Amgen Inc. or Janssen Products LP studies and published data for other studies. Random-effects odds ratios (OR) were calculated to compare results for patients randomized to ESA to patients randomized to control. Analyses were stratified by metastatic stage; mixed stage or treatment; and adjuvant/neoadjuvant treatment. Results: We analyzed 9 studies (N = 4713; ESA n = 2346, control n = 2367) (Table).The overall stratified random-effects OR for death was 1.17 (95% confidence interval, 0.99-1.39). Details are presented in the Table. Conclusions: Overall survival OR remains consistent with prior data after including recent results. [Table: see text]

e19630 Background: Chemotherapy-induced anemia has debilitating effects on patients with cancer. Treating anemia associated with chemotherapy and many cancers is often necessary. Epoetin therapy is...

20743 Background: To determine the efficacy and safety of epoetin beta in the prevention and treatment of anaemia in non-small cell lung cancer (NSCLC) patients treated with chemotherapy. Methods: ...

19605 Background: Epoetin beta administered three times weekly is effective in the treatment of anemia in patients with malignancy. This study investigated the efficacy and safety of a more convenient and reduced frequency administration of epoetin beta 30,000 IU sc once weekly in anemic patients with early or metastatic breast cancer receiving chemotherapy (CT). Methods: Patients >18 years with early or metastatic breast cancer receiving CT with hemoglobin (Hb) [Table: see text]

19588 Background: Anemia is the most frequent hematological complication of cancer. Epoetin beta (E), an effective treatment of anemia in patients with solid tumors (ST) was administered three-times weekly. However, the QW regimen used in patients with hematological malignancies would be more convenient and may improve patient compliance. The aim of our study was to evaluate efficacy and safety of E 30 000 IU QW in patients with ST. Methods: This study was an open-label, single-arm, multicenter trial carried out in 87 French centers between December 2003 and August 2005. Eligibility criteria were: informed consent, age =18 yrs, WHO performance status 0–2, malignant ST or non-myeloid hematological malignancy, on-going chemotherapy and anemia: hemoglobin (Hb) 11 g/dl at baseline respectively). Delay of Hb response, transfusion requirement, mood and cognitive functions were also assessed. Here we focus specifically on the subgroup of patients with ST. Results: In total, 365 patients with ST were included. The most frequent cancer sites were: lung (102 pts) and breast (86 pts). Median Hb level at baseline was 10.4 g/dl [7.9–12.3]. At endpoint, median Hb level increased to 12.5 g/dl [8.4–15.0]. Hb response rate (RR) was: 61% (IC95: 55–66%), 50% (IC95: 38–55%) in patients treated with platinum based regimen and 72% (IC95 : 62–76%) in patients treated without platinum. RR was 54% in lung (IC95: 44–64%), 76% in breast (IC95: 67- 85%). E treatment was well tolerated. Thromboembolic events occurred in 7% of patients, a rate consistent with information provided in the current label for E. Conclusion: Epoetin beta 30 000 IU once weekly is effective and well tolerated in anemic patients with solid tumor treated with chemotherapy. Once weekly treatment offers a convenient therapy which will improve patient compliance. [Table: see text]

15133 Background: Tumor-related or chemotherapy-induced anemia is common in gastrointestinal cancer patients and results in reduced quality of life and worse prognosis. Thus, the effectiveness of erythropoetin (epoetin beta) treatment (EB) to achieve and maintain a target haemoglobin (Hb) level of ≥ 11 g/dl was assessed within a randomised German AIO phase II study to assess efficacy of irinotecan/capecitabine versus cisplatin/capecitabine in advanced gastric or lower esophageal cancer. Methods: Patients (pts) with untreated locally advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction (KPS ≥ 60%, > one measurable lesion, adequate organ functions) were randomized to receive 3-weekly cycles of either irinotecan 250 mg/m2 d1 (arm A) or cisplatin 80 mg/m2 d1 (arm B). Capecitabine was administered at 2000 mg/m2 for 14 days in both arms. In both arms, EB (30,000 I.E. once weekly) was given at Hb of < 11 g/dl and continued until Hb ≥ 12 g/dl. If after 4 treatment weeks, Hb increase was < 0.5 g/dl, EB was increased to 30,000 I.E. twice weekly. FACT-An questionnaires were completed at each cycle. Results: At time of abstract submission, 81 pts were randomized to A (37 pts) or B (44 pts). 23 pts received at least 3 EB injections (A: 10 pts, B: 13 pts). Median Hb prior to EB was 10.5 g/dl (A: 10.4 g/dl, B: 10.5 g/dl) and median Hb at end of EB was 11.6 g/dl (A: 11.5 g/dl, B: 11.75 g/dl). During EB, 80 % of A and 77 % of B achieved target Hb of ≥ 11 g/dl with a median rise in Hb of 2.0 g/dl (A: 1.4 g/dl, B: 2 g/dl). 5 pts in A and 7 pts in B responded with a ≥ 1 g/dl rise in Hb during first 4 weeks. FACT-An questionnaires showed no change from baseline to end of EB. Among evaluable pts with EB (20 pts) versus without EB (34 pts), response (CR + PR) and tumor control rates (CR + PR + SD) were 60% vs 35% and 85% vs 70%, respectively. Conclusions: EB is effective in raising Hb levels in advanced or metastatic gastric cancer. Patients receiving EB tend to show a better response to chemotherapy. No significant financial relationships to disclose.

19582 Background: The efficacy of epoetin beta (E) is well documented in clinical trials in anemic cancer patients (pts). This study was conducted to assess E use, efficacy, safety and effect on quality of life in cancer pts, in usual practice. Methods: This prospective, multicenter, longitudinal, observational French study assessed a 4-month follow-up of informed consent cancer pts (including both solid tumors (ST) and hematological malignancies (H)) treated with E for chemotherapy-related anemia. Data were collected between January 2005 and March 2006. Results: Among 3100 pts enrolled by 423 specialists, 2810 were analysed. Pts’ characteristics were: mean age 63±13 yrs, male 50%, performance status 0 (13%), 1 (46%), =2 (41%). 74% of pts suffered from a ST and 26% from a H. The most frequent cancer types were lung (22%), breast (15%), non-Hodgkin lymphoma (12%), colon (9%), multiple myeloma (7%), ovary (7%), prostate (3%), head and neck (3%) and chronic lymphocytic leukemia (3%). The mean time from diagnosis to inclusion was 2 yrs. 52% of pts received their first line of chemotherapy, 25% their second one. 55% and 10% of ST and H pts received platinum based regimen, respectively. At inclusion, hemoglobin levels were distributed as follows: < 9 g/dl (ST 14%, H 32%), [9–11 [g/dl (ST 70%, H 56%), [11–13 [g/dl (ST 16%, H 11%). Regarding pre-treatment biological tests, endogenous erythropoietin rate was controlled for only 3% of pts (ST 1% and H 7%, median 37 IU/ml [0; 388]), ferritin was available for 15% of pts (ST 11% and H 28%), transferrin saturation for 12% of pts (ST 10% and H 17%) and reticulocytes for 11% of pts (ST 7% and H 24%). At initiation, pts received a median dose of 30000 U/week of E on a once weekly regimen schedule for 98% of pts. E was associated with iron supplementation in 49% and 13% of ST and H pts, and with blood transfusion in 5% and 15% of ST and H pts. Conclusion: These preliminary results describe baseline characteristics of cancer patients treated with epoetin beta. The study suggests very few biological controls before initiation of E in routine practice. Final analyses of hemoglobin evolution and quality of life will be presented. [Table: see text]

18620 Background: Anemia is common in patients receiving chemotherapy, causing a multitude of symptoms which have a major impact on quality of life (QoL). Epoetin beta rapidly increases hemoglobin (Hb) levels and improves QoL in anemic patients with a variety of tumors. In patients with lymphoid malignancies, once-weekly epoetin beta 30,000 IU has comparable efficacy to the three-times weekly 10,000 IU regimen (Cazzola et al. Br J Haematol 2003; 122: 386–393). Methods: This was a randomized, double-blind, dose-finding study assessing the efficacy and safety of once-weekly epoetin beta in patients with solid tumors receiving chemotherapy. Adult patients with anemia (Hb levels No significant financial relationships to disclose.

18548 Background: Direct comparison of EA vs EB vs DE has never been performed. In order to define the efficacy, impact on quality of life (QL) and pt’s preference, a prospective observational comparison of erythropoietic agents has been carried out. Methods: Anemic pts (hgb 9,5; PS ≤0–1 vs >1; previous CT vs upfront CT; and previous antianemic therapy vs not) and were autonomously assigned by 15 investigators to EA (3 times a week) or EB (3 times a week and only in pts receiving platinum-based CT) or DE (once a week) therapy. Efficacy by hgb level changes and transfusion needing was evaluated after each cycle of CT, QL by Fact-An questionnaire after 1 and 3 cycles of CT, and pt’s preference for standard vs weekly schedule at least once thereafter. Results: From 09/04 to 12/05 177 pts were recruited: 41%, 39% and 20% were assigned to DE, EA and EB, respectively. Severe anemia at baseline (≤9,5) was reported in 29% of pts, whereas 47% received platinum-based CT. Stratifying categories were well balanced among the treatment groups. Baseline mean hgb values were 9.7, 9.9, and 10 for DE, EA and EB, respectively. As of the general population, DE produced higher subsequent mean hgb increase in respect to EA and EB (Mean increase [gr/dL] for DE: 0.84, 1.58, 2.03; EA: 0.34, 0.84, 1.68; EB: 0.76, 1.54, 1.17). No difference was observed neither among pts receiving platinum-based CT, (mean increase: DE: 0.34, 1.76, 2.8; EA: 0.7, 1.27, 2.14; EB: 0.76, 1.54, 1.71) nor among pts with severe anemia at baseline (DE: 0.98, 2, 2.6; EA: 1.24, 1.94, 3.13; EB: 1.25, 2.25, 2.75). Transfusion needing ranged from 7% for DE to 3% for EB without any significant difference. To date 67% of pts completed at least one subsequent QL valuation, whereas 62% gave their preference for treatment schedule. Conclusions: Early results of our prospective analysis show that antianemic therapy with D is at least as effective as standard schedule of EA or EB. Efficacy of DE seems confirmed in pts with bad prognostic categories for anemia. Major data on QL and pt’s preference will be presented. No significant financial relationships to disclose.

8230 Background: The aim of this study was to determine whether epoetin treatment in solid tumor patients receiving platinum (Pt)-based chemotherapy (CT) might prevent anemia and improve patients’ ...

8141 Background: Many patients with metastatic breast cancer are treated with anthracycline and/or taxane-based chemotherapy; such therapies produce a high incidence of anemia. The aim of the BRAVE...

5102 Background: Recent meta-analyses in anemic patients with cancer have shown that epoetins do not have a negative impact on survival and show a trend towards reducing the risk of disease progres...

5121 Background: Patients with advanced cervical cancer frequently suffer from anaemia. Additionally, concomitant anaemia is aggravated by radiochemotherapy (RCT). Study Objectives: This study aime...

8169 Background: Administering epoetin beta (EPO) to anemic cancer patients receiving chemotherapy has been reported to improve their anemia and quality of life (QOL). We conducted a randomized, do...

8206 Background: The dose of Erythropoietin for chemotherapy-induced anemia in cancer patients is considerably higher than the one used for anemia due to renal failure. However, limited number of reports on pharmacokinetics (PK) with higher dose are available. We carried out the PK and pharmacodynamic study of epoetin beta (EPOCH) in lung cancer (LC) patients with chemotherapy-induced anemia. Methods: Fifteen LC patients with chemotherapy-induced anemia [hemoglobin (Hb) level of 11 g/dL or less] received EPOCH 9000, 18000 or 36000 IU subcutaneously (SC), weekly for 8 weeks. We estimated the PK parameters following the first administration of EPOCH and also measured the trough level of Erythropoietin and Hb level over 7 weeks. Results: Cmax and AUC rose in proportion to the dose given, and T\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \({1}/{2}\) \end{document}, Vd, and CL appeared almost stable ...