Darbepoetin alfa Administered Every 3 Weeks Is Effective in Correcting Hemoglobin and Reducing Transfusion Requirements in Anemic Patients with Hematological Malignancies Receiving Chemotherapy: A Retrospective Observational Study Reflecting Real-World Clinical Practice in Europe.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4085-4085
Author(s):  
Bertrand Coiffier ◽  
David Coeffic ◽  
Frank Strohbach ◽  
Marcus Schweigert ◽  
Hirsh Koyi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Practice ◽  
Real World ◽  
Darbepoetin Alfa ◽  
Hematological Malignancies ◽  
Hematologic Malignancies ◽  
Tumor Type ◽  
Phase 3 ◽  
End Of Treatment ◽  
Hematopoietic Response

Abstract Introduction: Observational research provides valuable comparative information about the use and effect of drugs in a particular patient (pt) population (eg, pts with hematological malignancies) in real-world clinical practice, which may be different from those in controlled clinical studies. Methods: This multicenter study of medical records evaluated use of darbepoetin alfa (DA) 500 mcg every 3 weeks (Q3W) in anemic pts with nonmyeloid malignancies receiving chemotherapy treatment in 7 European countries (Denmark, France, Germany, Greece, Spain, Sweden, and Switzerland). Data were collected on a retrospective basis using medical record review and a standard case report form. Data related to adverse events or other measures of safety were not collected. The analysis included pts who either completed the observational period (≤16 weeks) or stopped treatment but received ≥1 DA dose. Pts had to be ≥18 years old, start DA treatment after 01January2004, and provide informed consent (if needed by country regulations). Descriptive statistics were generated. In this posthoc analysis, a subset analysis was performed by tumor type: hematologic malignancies, solid tumors, and all pts. Percentages of pts with hematopoietic response (hemoglobin [Hb]≥12g/dL and/or 2-g/dL increase from baseline to end of treatment period), transfusion, and Hb ≥11 g/dL were evaluated. Results: 391 pts received DA, of whom 64 (20%) had hematologic malignancies. Overall, most pts were women (60%) and white (97%), with a mean (SD) age of 62.5[11.8] yrs and a mean baseline Hb of 9.7[0.9] g/dL. Most pts received concomitant chemotherapy (99%). No pts discontinued treatment due to side effects. In pts with hematologic malignancies, treatment with DA 500 mcg Q3W increased Hb levels above 11 g/dL in 73% of patients and left 69% of pts transfusion free (Table). These results were similar in pts with other tumor types and in all pts in this study, as well as in pts with lymphoproliferative malignancies enrolled in previously reported phase 3 clinical trial of the DA QW treatment schedule (Table). Table. Outcomes Real-world Study (DA 500mcg Q3W) Phase 3 Study Kaplan Meier proportions of patients (95% Confidence Intervals) # Hematologic Malignancies (n=64) Other Tumors (n=261) All Pts (n=325) DA 2.25 mcg/kg QW (n=174) Placebo (n=170) NR=not reported; #=Based on effectiveness analysis set. Phase 3 Study = Hedenus et al, Brit J Haematol2003;122:394. Hematopoietic response 59%(44–73) 68%(60–75) 66%(59–73) 65%(57–73) 24%(72–81) Hemoglobin ≥11g/dL during study 73%(61–85) 85%(78–92) 78%(71–85) NR NR At least 1 transfusion (week 5 to end of treatment period) 31%(18–44) 22%(16–29) 24%(19–30) 31%(24–38) 48%(41–56) Conclusion: Based on these results, DA 500 mcg Q3W in real-world clinical practice in Europe exhibited similar effectiveness compared with outcomes observed in clinical trial setting. In this study, DA 500 mcg Q3W appeared to be effective in treating anemia in pts receiving chemotherapy, regardless of tumor type.

Use and Outcomes of Epoetin Alfa and Darbepoetin Alfa for Anemic Cancer Patients in Outpatient Community Practice Settings.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5588-5588 ◽  
Author(s):  
Kyle R. Fahrbach ◽  
Diana Frame ◽  
Brian Sercus ◽  
Brad Schenkel
Keyword(s):  
Cancer Patients ◽  
Darbepoetin Alfa ◽  
Selection Criteria ◽  
Tumor Type ◽  
Community Practice ◽  
Epoetin Alfa ◽  
Treatment Episode ◽  
End Of Treatment ◽  
Dosing Regimens ◽  
The Cost

Abstract Objective: To assess the treatment patterns and hematologic outcomes associated with epoetin alfa (EPO) and darbepoetin alfa (DARB) for the treatment of anemic cancer patients in the community practice setting. Methods: A retrospective observational study design was used. De-identified data from patients receiving care in community oncology practice settings were obtained from an electronic medical record system. Eligible patients were >= 18 years of age, had a cancer diagnosis, and were treated with an erythropoiesis stimulating agent (ESA: EPO or DARB) during the period July 2002 – July 2004, with baseline anemia (Hb<=11 g/dL) and at least one follow-up Hb value. No other selection criteria were applied (e.g. ESA dose, tumor type, chemotherapy treatment) in keeping with the objective of characterizing outcomes in a real-world setting. Data were summarized by treatment overall and by using a multivariate model adjusting for age, gender, baseline Hb, clinic site, ECOG performance score, type of cancer (solid vs hematologic) and chemotherapy (platinum vs non-platinum vs. none). Patient selection criteria and analytic methods were determined prospectively. The cost for each ESA was calculated based on 2004 average wholesale prices ($13.36 per EPO 1,000 U; $4.99 per 1 mcg DARB). Results: 2382 EPO and 1399 DARB patients were eligible for analysis. The two groups were comparable in terms of baseline characteristics (62% female, 75% solid tumors, mean baseline Hb 9.9 g/dL). Only about two-thirds of patients were treated with standard dosing regimens of the two agents in the US (EPO 40,000 U qw, DARB 200 mcg q2w). Hematologic outcomes observed in patients receiving EPO were consistently better than those in patients receiving DARB. Table 1. Hematologic outcomes by ESA treatment EPO DARB p value Week 4 Hb change (g/dL) 0.79 0.59 <0.001 % Early Hb response (Hb change >=1 g/dL at 4 weeks) 61.5 55.2 0.004 % Hb response (Hb change >=2 g/dL by end of treatment episode) 41.4 34.7 <0.001 % Hematopoietic response (Hb change >= 2 g/dL or reaching 12 g/dL by end of treatment episode) 52.3 44.6 <0.001 The mean treatment durations for patients receiving EPO and DARB were 55.3 and 62.5 days, respectively. Mean cumulative doses were 231,211 U for EPO and 857 mcg for DARB. These doses resulted in an average cost per patient of $3,089 for those receiving EPO and $4,276 for those receiving DARB. Conclusion: These results, based on over 3000 community-treated cancer patients, reinforce previous findings of earlier and greater overall hematologic response for EPO vs. DARB in this setting. Additionally, based on mean cumulative doses, the cost of DARB per patient was substantially greater than that of EPO. Additional studies of variations in dosing regimens used in the community setting are warranted, as are well-powered, randomized, controlled trials to further confirm the clinical results observed here.

Assessing real-world clinical response in patients with multiple myeloma (MM): A survey of the literature.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19260-e19260
Author(s):  
Daniel Lane ◽  
Andrew D. Norden ◽  
Andrew J. Belli ◽  
Ching-Kun Wang
Keyword(s):  
Clinical Trial ◽  
Clinical Practice ◽  
Real World ◽  
English Language ◽  
Complete Response ◽  
Protein Electrophoresis ◽  
Mandatory Reporting ◽  
Routine Clinical Practice ◽  
Cell Transplant ◽  
Strict Adherence

e19260 Background: A recent study (Foster, Tromanhauser et al. 2019) utilizing Electronic Health Record (EHR) data found that patients with MM rarely have both serum protein electrophoresis (SPEP) and 24-hour urine protein electrophoresis (UPEP) documented in routine clinical practice settings. These elements are necessary to classify response using the International Myeloma Working Group (IMWG) consensus criteria. It could be hypothesized that adding the additional requirements for bone marrow biopsy necessary to confirm a complete response would further reduce the rate of strict adherence to the IMWG criteria in the real world (RW). Clinicians are however assessing response and progression in RW settings and often report these assessments in published literature. In this study, we survey the literature to determine how RW response is being captured and reported outside of the clinical trial setting. Methods: A systematic search was performed using Medline 2010-2019. Using a standardized grading system, English language articles were evaluated that utilized EHR data from routine clinical practice to report RW response in patients with active MM. Registry based and/or pragmatic observational studies were excluded as many had mandatory reporting procedures in place. Studies were then categorized based on methods of assessing response, progression and use of IMWG criteria. Results: The majority of studies grade 1 studies identified (21/25) utilized best response achieved based on treating physician-documented assessment and either did not specify the use of IMWG(10/21) criteria or explicitly stated they did not use conventional criteria (11/21). Progression event capture and reporting varied greatly with many using physician-documented progression, change in regimen, addition of additional agents to existing regimen, stem cell transplant, or an individually created algorithm. Conclusions: Our findings suggest that there is a need for further research on objective techniques for the assessment of RW progression and response in patients with MM. Additionally, validation of an approach that utilizes partial adherence to IMWG criteria would help in the ability to compare findings across clinical trial and RW settings. This validation work is under way, and preliminary results will be reported at the meeting.

Evaluation of clinical use of darbepoetin alfa in patients with chemotherapy-induced anemia

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20585-e20585
Author(s):  
A. Bustos ◽  
M. A. Cruz ◽  
P. Aramburo ◽  
F. Carabantes ◽  
N. Díaz ◽  
...  
Keyword(s):  
Adverse Event ◽  
Darbepoetin Alfa ◽  
Clinical Characteristics ◽  
Treatment Initiation ◽  
Real Life ◽  
Clinical Use ◽  
Patterns Of Use ◽  
End Of Treatment ◽  
Hematopoietic Response ◽  
Retrospective Multicenter Study

e20585 Background: Chemotherapy-induced anemia (CIA) is a frequent complication of patients (pts) with cancer and could be treated with erythropoiesis-stimulating agents such darbepoetin alfa (DA). The aim of this study was to investigate the patterns of use and effect of DA to treat CIA in clinical practice conditions. Methods: This was an observational, retrospective, multicenter study performed in 58 Spanish centres. Eligible pts were ≥18 yrs, diagnosed with non-myeloid malignancies and treated with chemotherapy (CT) and DA from October 2005 to October 2006. Data on demographic and clinical characteristics, CT and radiotherapy (RT), DA administration, red blood cell (RBC) transfusions, and haemoglobin (Hb) levels were collected from DA treatment initiation up to a maximum of 16 weeks or until treatment discontinuation. Results: A total of 685 pts were included in the study. Median age was 64.66 years (range 18.54–88.95), 50.7% were women, 74.11% had ECOG status 0–1 and 71.38% had stage III/IV cancer. Solid tumours represented 72.55% of the cases. The CT regimen included platinum derivates in 33.58% of the pts. At DA initiation, mean (SD) Hb was 10.00 g/dL (1.05) Administration of DA every three weeks occurred in 54.01% of the pts. Mean (SD) DA administration was 9.20 weeks (5.31). Hematopoietic response (defined as Hb ≥ 12 g/dL or Hb rise from baseline >2 g/dL in the absence of RBC transfusions during the previous 28 days) occurred in 63.24% (95% CI 59.49–66.83) of pts. A total of 88 pts (12.85%) required RBC transfusions from week 5 to end of treatment. Mean Hb (SD) at the end of treatment with DA was 11.36 g/dL (1.73). Adverse event (AE) potentially related to DA were reported in 20 pts (2.92%) and considered severe in 6 cases (0.88%). Conclusions: The findings of this study indicate that the use of DA for the treatment of CIA in real-life, daily oncology and haematology practice, is well-tolerated and effective for increasing haemoglobin to reduce the need of RBC transfusions. [Table: see text]

A Prospective, Observational Study of the Effectiveness and Safety of a Weekly Fixed Dose of Darbepoetin alfa with Current Practice Iron Management for the Treatment of Chemotherapy-Induced Anemia (CIA): A Subanalysis in Patients (pts) with Lymphoproliferative Malignancies (LPM).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3715-3715
Author(s):  
A. Alegre ◽  
A. Salar ◽  
I. Roig ◽  
J.C. Bermejo ◽  
A. Palacios ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Iron Deficiency ◽  
Darbepoetin Alfa ◽  
Iron Status ◽  
Oral Iron ◽  
Fixed Dose ◽  
Fatigue Score ◽  
Absolute Iron Deficiency ◽  
The Impact ◽  
Hematopoietic Response

Abstract Background: Darbepoetin alfa (Aranesp®) is a unique erythropoiesis-stimulating protein effective for the treatment of CIA when administered weekly (QW), every 2 weeks (wks) or every 3 wks. Fixed dosing of darbepoetin alfa is routinely used in clinical practice, but little data are available on its patterns of use and the impact of iron status on its effectiveness. Methods: This was a subanalysis of LPM pts included in a prospective, single-arm, multicenter study conducted in Spain. Pts were ≥ 18 yrs old, anemic (hemoglobin [Hb] ≤11 g/dL), scheduled to receive ≥ 12 wks of chemotherapy, and without iron, vitamin B12, or folate deficiencies. Pts were treated with darbepoetin alfa 150 mcg QW; the dose was to be doubled to 300 mcg QW if Hb increased <1 g/dL after 4 wks. Oral iron (200 mg QD) was recommended if transferrin saturation was ≤ 30%, transferrin was ≥ 400 mcg/dL, and/or ferritin was ≤ 300 mcg/L at any time during the study. The primary endpoint was hematopoietic response (Hb increase ≥ 2 g/dL or Hb ≥ 12g/dL in the absence of transfusions in the previous 28 days). Secondary endpoints included the percentage of pts with functional or absolute iron deficiency and its correlation with response rates, change in FACT-Fatigue score from baseline to end of treatment (EOT), and safety. Results: Of a total of 293 patients enrolled, 129 had LPM and were included in this analysis. Of the LPM patients, 55% were women, median age was 67.3 yrs (range: 20.6–88.4), median weight was 67 kg (range: 40.5–115.0). Eleven percent had Hodgkin’s disease, 33.9% had non-Hodgkin’s lymphoma. 5.5% had chronic lymphocytic leukemia, and 49.6% had multiple myeloma. Most pts (80.5%) had baseline Hb between 9–11 g/dL; 19.5 % had Hb < 9 g/dL. Darbepoetin alfa was administered for a median of 16 wks (range:1–16). At wk 5, 25.6 % of pts had their dose doubled to 300 mcg QW. The observed hematopoietic response was 70.73% (95%CI: 62.69, 78.77). The proportion of pts transfused from wk 5 to EOT was 12.7%. During the study, 31.5% pts received oral iron, 10.3% developed absolute iron deficiency, and 8% had iron blockade. Mean (95% CI) FACT-Fatigue score increased from 34.1 (32.2, 35.9) to 40.0 (38.2, 41.8) (p<0.0001). Darbepoetin alfa was well tolerated with 2.4% of pts experiencing adverse events considered related to the study drug. Conclusions: darbepoetin alfa, given as a fixed dose, is an effective and well-tolerated treatment for CIA in pts with LPM. Darbepoetin alfa significantly improved health-related quality of life in this routine clinical practice setting.

Palifermin Reduces Estimated Downstream Costs of Autologous Stem Cell Transplant (SCT): Analysis of Phase 3 Trial Results.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2191-2191 ◽  
Author(s):  
L.S. Elting ◽  
Y.C.T. Shih ◽  
P.J. Stiff ◽  
W. Bensinger ◽  
S.B. Cantor ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Oral Mucositis ◽  
Hospital Costs ◽  
Hematologic Malignancies ◽  
Cell Transplant ◽  
Phase 3 ◽  
The Mean ◽  
The Cost ◽  
Hospital Days ◽  
Mean Cost

Abstract Introduction: Oral mucositis is a frequent and debilitating complication in patients (pts) who undergo high-dose chemotherapy (HDC) with SCT support and is associated with significantly worse clinical and economic outcomes in such settings (Sonis et al, J Clin Oncol, 2001). In a phase 3 randomized, placebo-controlled, double-blind clinical trial of palifermin in pts with hematologic malignancies undergoing HDC and total body irradiation (TBI) with auto-SCT support, palifermin (a rHuKGF molecule) has been shown to reduce the incidence, severity, and duration of oral mucositis as well as its downstream outcomes (bacteremia, febrile neutropenia [FN], total parenteral nutrition [TPN], and intubation) and hospitalization in this population (Spielberger, et al, ASCO, 2003). We estimated the expected impact of palifermin on the hospital costs of transplantation. Methods: We classified the 212 pts from the phase 3 trial by presence of downstream outcomes of oral mucositis (bacteremia, FN, TPN, intubation) and by the number of hospital days. The cost of hospital days was not collected in the clinical trial, hence, we estimated cost from the hospital claims of a nationally representative sample of pts with hematologic malignancies who underwent auto-SCT after TBI. We obtained charges from the National Inpatient Sample (NIS, 2000–2001), transformed them into costs using state-specific Medicare cost-to-charge ratios for operating and capital costs for urban centers, and adjusted them to 2003 U.S. dollars using the Consumer Price Index for medical care. We computed the mean cost per hospital day for NIS pts with 0, one, or more of the 4 downstream outcomes (FN, bacteremia, TPN, intubation), and applied these costs to the number of hospital days of clinical trial pts with corresponding downstream outcomes. We compared the estimated total hospital costs of palifermin pts to placebo pts. Out-pt costs of SCT were not estimated and the cost of palifermin has not yet been determined, therefore neither was included in this analysis. Results: The age and sex distributions of NIS and clinical trial pts were virtually identical as were the mean hospital days (22.52 vs. 22.87 days), but non-Hispanic whites were more common in the clinical trial population (79% vs. 63%). In pts with hematologic malignancies, the national mean cost per hospital day for auto SCT after TBI was $2,702, ranging from $2,572 per day when no downstream outcomes occurred to > $5,000 per day when all 4 downstream outcomes occurred. Applying these differing costs to the differing outcomes of clinical trial pts, the mean cost per pt was $61,160 with palifermin and $76,104 with placebo, yielding a mean savings of $14,943 per pt (95% CI: $12,043–$17,845) in this population. Savings will be partially offset by the cost of palifermin and may vary among centers, particularly those that perform outpatient transplants. Extrapolations of these data to the allogeneic and autologous non-TBI settings also will be presented. Conclusion: The clinical efficacy of palifermin should lead to significant hospital cost savings for pts with hematologic malignancies undergoing auto-SCT following HDC and TBI. The magnitude of savings will depend on the cost of the drug.

Correction/Maintenance Dosing (Front Loading) of Darbepoetin alfa: Final Results from a Randomized Phase 3 Active Controlled Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1636-1636 ◽  
Author(s):  
D. Kotasek ◽  
J.-L. Canon ◽  
J. San Miguel ◽  
M. Hedenus ◽  
L. Hendricks ◽  
...  
Keyword(s):  
Treatment Period ◽  
Primary Endpoint ◽  
Darbepoetin Alfa ◽  
Controlled Trial ◽  
Pilot Studies ◽  
Entire Study ◽  
End Of Treatment ◽  
Transfusion Requirements ◽  
Hematopoietic Response ◽  
Maintenance Group

Abstract Prior research with darbepoetin alfa (DA; Aranesp®) in patients with chemotherapy-induced anemia (CIA) has indicated the possibility of decreasing the time to response through the use of higher initial doses (4.5 mcg/kg once weekly [QW]) compared with standard dosing regimens (either of DA or epoetin alfa [Procrit®]). Research has also shown that an every 3 week (Q3W) dosing schedule of DA is effective in alleviating the symptoms of CIA. Pilot studies using a correction/maintenance approach (‘front loading’) have combined these two potentially attractive clinical attributes. This active-controlled trial examined the efficacy of DA using a correction/maintenance dosing regimen in patients with nonmyeloid malignancies receiving chemotherapy. In this study, 727 anemic patients (hemoglobin [Hb] <11g/dL) were randomized 1:1 to receive a DA dose of either 2.25 mcg/kg QW for 16 weeks or 4.5 mcg/kg QW for weeks 1–4, followed by a Q3W maintenance regimen using the same dose (4.5 mcg/kg) for weeks 5–16. The primary endpoint was to demonstrate the non-inferiority of correction/maintenance dosing versus standard weekly dosing, with respect to the proportion of patients either requiring a transfusion or withdrawing from the study during the 16-week treatment period. The pre-specified, non-inferiority margin, based on the effect size observed in DA placebo-controlled trials, was 12.5%. The two treatment groups were well balanced for baseline characteristics: 32% had hematologic malignancies, 15% breast cancer and 13% lung cancer. Both groups had a mean (SD) baseline Hb of 9.6 (1.0) g/dL. Non-inferiority was demonstrated with respect to the primary endpoint with a mean (95% CL) difference between groups of 1% (−7, 9). No difference was observed for the proportion of patients receiving a RBC transfusion from week 5 to end of treatment [24% (19, 28) for the 2.25 mcg/kg QW group vs 25% (20, 30) for the correction/maintenance group]. Over the entire study period, 87% (83, 91) of patients in the DA 2.25 mcg/kg group achieved a hematopoietic response at the end of treatment compared with 68% (62, 73) in the correction/maintenance group, suggesting no additional benefit for correction/maintenance dosing compared with standard dosing. During the initial 7 weeks of study, no differences were observed between patients receiving 2.25 mcg/kg QW or 4.5 mcg/kg QW for any endpoint (eg, Hb change of 1.4 g/dL after 6 weeks in both groups); Q3W dosing at 4.5 mcg/kg was shown to be effective in maintaining Hb through the remainder of the treatment period. No difference in adverse events between the two groups was observed. DA 2.25 mcg/kg QW is highly effective with respect to the reduction of transfusion requirements and management of anemia symptoms in patients with CIA. In this study of anemic patients with nonmyeloid malignancies receiving chemotherapy, almost all patients in the 2.25 mcg/kg QW dose group achieved a hematopoietic response, offering little room for additional clinical benefit that may have been expected in the 4.5 mcg/kg QW group as a result of the increased dose. Q3W dosing with DA 4.5 mcg/kg was shown to effectively maintain Hb levels. The effectiveness of lower/less frequent doses cannot be determined from this trial.

Challenges in Using Real-World Clinical Practice Records for Retrospective Validation of Clinical Trial Data: Lessons Learned

2016 ◽  
Vol 111 ◽  
pp. S324-S325
Author(s):  
Sunanda V. Kane ◽  
Anita Afzali ◽  
Doug Wolf ◽  
Ira Shafran ◽  
Matthew A. Ciorba ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Practice ◽  
Real World ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Lessons Learned
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