Beatriz Pujol

Darbepoetin alfa for treating chemotherapy-induced anemia in patients with a baseline hemoglobin level < 10 g/dL versus ≥10 g/dL: an exploratory analysis from a randomized, double-blind, active-controlled trial

BackgroundSeveral studies have shown that darbepoetin alfa, an erythropoiesis-stimulating agent (ESA), can reduce transfusions and increase hemoglobin (Hb) levels in patients with chemotherapy-induced anemia (CIA). Recent safety concerns, however, have prompted changes to ESA product information. In the European Union and United States, ESA therapy initiation for CIA is now recommended at a Hb level ≤10 g/dL. The present exploratory analysis examined how ESA initiation at this Hb level may impact patient care.MethodsData from a phase 3 randomized trial were retrospectively reanalyzed. CIA patients with nonmyeloid malignancies were randomized 1:1 to 500 mcg darbepoetin alfa every three weeks (Q3W) or 2.25 mcg/kg darbepoetin alfa weekly (QW) for 15 weeks. A previously published report from this trial showed Q3W dosing was non-inferior to QW dosing for reducing transfusions from week 5 to end-of-the-treatment period (EOTP). In the present analysis, outcomes were reanalyzed by baseline Hb <10 g/dL and ≥10 g/dL. Endpoints included transfusion rates, Hb outcomes, and safety profiles.ResultsThis study reanalyzed 351 and 354 patients who initiated ESA therapy at a baseline Hb of <10 g/dL or ≥10 g/dL, respectively. From week 5 to EOTP, the estimated Kaplan-Meier transfusion incidence (Q3W vs QW) was lower in the ≥10 g/dL baseline-Hb group (14% vs 21%) compared with the <10 g/dL baseline-Hb group (36% vs 41%). By week 5, the ≥10 g/dL baseline-Hb group, but not the <10 g/dL baseline-Hb group, achieved a mean Hb ≥11 g/dL. The Kaplan-Meier estimate of percentage of patients (Q3W vs QW) who achieved Hb ≥11 g/dL from week 1 to EOTP was 90% vs 85% in the ≥10 g/dL baseline-Hb group and 54% vs 57% in the <10 g/dL baseline-Hb group. Both baseline-Hb groups maintained mean Hb levels <12 g/dL and had similar safety profiles, though more patients in the ≥10 g/dL baseline-Hb group reached the threshold Hb of ≥13 g/dL.ConclusionIn this exploratory analysis, darbepoetin alfa Q3W and QW raised Hb levels and maintained mean Hb at <12 g/dL in both baseline-Hb groups. The ≥10 g/dL baseline-Hb group had fewer transfusions and faster anemia correction. Additional studies should prospectively evaluate the relationship between Hb levels at ESA initiation and outcomes.Trial RegistrationClinicalTrials.gov Identifier NCT00118638.

Anemia and erythropoiesis-stimulating agent administration in patients with non-Hodgkin lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone ± rituximab chemotherapy: results from an observational study.

CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) ± rituximab [(±R)CHOP] is the current standard of care for aggressive non-Hodgkin lymphoma (NHL). Anemia resulting from chemotherapy can be treated with erythropoiesis-stimulating agents (ESAs). As part of the observational IMPACT NHL study, data were collected on ESA use and anemia-related outcomes in 1829 adults receiving (±R)CHOP-14 or (±R)CHOP-21. Overall, 33% of patients were anemic during chemotherapy. Older age, lower baseline hemoglobin (Hb), worse performance status, more advanced disease stage, and use of CHOP-14 were significant predictors of transfusion and anemia in logistic regression models. ESAs were received by 404 patients, usually in response to low or declining Hb levels. Most patients (65%) had Hb 9–11 g/dL at ESA initiation, and 89% (Kaplan–Meier percentage) achieved Hb 10–12 g/dL. In conclusion, two-thirds of anemic patients with NHL receiving (±R)CHOP initiated ESA treatment at Hb 9–11 g/dL, and most achieved target Hb levels (10–12 g/dL).

Use of darbepoetin alfa in European clinical practice for the management of chemotherapy-induced anaemia in four tumour types: final data from the CHOICE study.

Abstract Objectives: The CHOICE study was a prospective, multicentre, observational study designed to assess levels of adherence in current clinical practice to the European product label and EORTC guidelines for the treatment of chemotherapy-induced anaemia (CIA) with darbepoetin alfa (DA). Here we present data split by tumour types: breast, colorectal, ovarian and lung. Methods: Haemoglobin (Hb) levels and red blood cell transfusion requirements were evaluated among patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10–≤12 g/dL. Results: The full analysis set included 1887 patients (mean ± SD 62.4 ± 11.4 years); 1585 (84%) had a current disease stage of ≥3. Common chemotherapy regimens were non-platinum + non-taxane based (n = 696 [37%]) or platinum + non-taxane based (n = 660 [35%]). Breast cancer (n = 575): The mean ± SD Hb level at baseline was 9.9 ± 0.8 g/dL (n = 568). Target Hb level was reached by 187 (55%) patients. Colorectal cancer (n = 310): At baseline the mean ± SD Hb level was 9.8 ± 0.8 g/dL (n = 306). Target Hb level was reached by 107 patients (56%). Ovarian cancer (n = 301): The mean ± SD Hb level at baseline was 9.7 ± 0.8 g/dL (n = 294). Target Hb level was reached by 81 patients (44%). Lung cancer (n = 701): At baseline the mean ± SD Hb level was 9.8 ± 0.9 g/dL (n = 692). Target Hb level was reached by 142 patients (39%). Safety: Five severe or life-threatening adverse drug reactions were seen (three patients with breast cancer, one patient with colorectal cancer and one patient with ovarian cancer). Limitations: Potential bias could not be excluded due to the study’s observational nature. Conclusions: This study demonstrates that the recommendations are adhered to in clinical practice, with the mean starting Hb level <10 g/dL irrespective of tumour type. Furthermore, DA is likely to be effective and well tolerated for the treatment of CIA in patients with breast, colorectal, ovarian or lung cancer.

A final analysis from the CHOICE study examining darbepoetin alfa use for chemotherapy-induced anaemia in current European clinical practice

Abstract Objectives: The CHOICE study was a prospective, multicentre, observational study designed to assess the level of adherence in current clinical practice to the European product label and the EORTC guidelines for the treatment of chemotherapy-induced anaemia with darbepoetin alfa (DA). Methods: Hb levels and red blood cell (RBC) transfusion requirements were evaluated among 1900 patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10–≤12 g/dL after 9 weeks’ DA treatment. Results: The full analysis set (FAS) comprised 1887 patients (mean ± SD age 62.4 ± 11.4 years) divided into categories by baseline Hb < 9 g/dL (n = 281); 9–<10 g/dL (n = 770); 10–<11 g/dL (n = 695); ≥11 g/dL (n = 114). The proportion of patients who remained on the study at week 9 achieving the target Hb level was 37% (n = 60), 48% (n = 217), 54% (n = 210) and 38% (n = 23) in the subgroups with a baseline Hb level of <9 g/dL, 9–<10 g/dL, 10–<11 g/dL and ≥11 g/dL, respectively. In the <9 g/dL, 9–<10 g/dL, 10–<11 g/dL and ≥11 g/dL subgroups of the FAS, the number of patients maintaining Hb levels ≥10 g/dL after their first achievement of an Hb value of 10 g/dL was 95 (34%), 372 (48%), 476 (68%) and 87 (76%), respectively. The Kaplan–Meier percentages of patients who required an RBC transfusion from week 5 until end of treatment period were: 29%, 20%, 12% and 17% in the <9 g/dL, 9–<10 g/dL, 10–<11 g/dL and ≥11 g/dL subgroups, respectively. Kaplan–Meier percentages of patients reaching an Hb level of >13 g/dL were 10%, 9%, 21% and 29%, respectively. Potential bias could not be excluded due to the study’s observational nature. Conclusions: DA initiation and target Hb ranges adhered to current guidelines in the majority of patients. Furthermore, this study demonstrates faster achievement of the target range and reduced transfusion requirements are associated with initiation of DA at Hb levels of 9–<10 g/dL and 10–<11 g/dL rather than <9 g/dL.

Cost analysis: treatment of chemotherapy-induced anemia with erythropoiesis-stimulating agents in five European countries

Abstract Objective: Cost-analysis comparing darbepoetin-alfa (DARB), epoetin-alfa (EPO-A), and epoetin-beta (EPO-B) for treatment of chemotherapy-induced anemia in Belgium concluded that costs for DARB-treated patients were significantly lower than costs for EPO-A- or EPO-B-treated patients. The objective of the present study was to extend the Belgian analysis to Austria, France, Italy, Portugal, and Spain, estimating differences in costs between erythropoiesis-stimulating agents (ESAs) in each country. Methods: Differences in epidemiology and treatment patterns between countries were adjusted using data from Eurostat, national cancer registries, IMS sales data, and reimbursement and treatment guidelines. Belgian unit costs were replaced with country-specific costs. Costs were analyzed using a mixed-effects model stratifying for propensity score quintiles. Results: All populations were comparable to the Belgian population in terms of age, gender, ESA, and blood transfusions use. After adjusting for country-specific chemotherapy use and cancer incidence, total management costs per patient (Euro, 2010) were 19–26% (France, Spain) lower with DARB compared with EPO-A (p < 0.0001) and 20–36% (Portugal, Austria) compared with EPO-B (p < 0.01). Anemia-related costs with DARB were between 12% (Portugal; p = 0.0235) and 38% (Italy; p < 0.0001) lower compared with EPO-A (p < 0.01; all remaining countries), and between 13% (Austria; p = 0.064) and 19% (Portugal; p = 0.0028) lower compared with EPO-B (p < 0.05; all remaining countries except Italy; p = 0.0935). Limitations: Not all differences could be accounted for by a lack of country-specific data; however, the potential under- and over-estimation of costs should be similar for all three ESAs. Conclusions: These findings are in line with the Belgian analysis. In all countries, total and anemia-related costs were lowest in patients receiving DARB vs EPO-A or EPO-B. This study demonstrates the feasibility of adapting real-life country-specific data to other settings, adjusting for differences in patients’ characteristics and treatment strategies. These findings should be valuable in healthcare decision-making in oncology patients treated in each of the countries studied.

Current practice of darbepoetin alfa in the management of haemoglobin levels in cancer patients undergoing chemotherapy – data from the CHOICE study

Abstract Objective: To evaluate adherence to European Organisation for Research and Treatment of Cancer (EORTC) and European Summary of Product Characteristic (SmPC) guidance on recommended haemoglobin (Hb) values in routine clinical practice use of darbepoetin alfa (DA) in cancer patients internationally. Methods: This multicentre, prospective, observational study assessed DA use in 11 European countries. This interim analysis (IA) included ∼1300 breast, colorectal, ovarian or lung cancer patients receiving DA during any chemotherapy cycle. Hb level and red blood cell (RBC) transfusion requirement data were collected. Results: Of the 1290 patients (mean [SD] age 62.5 [11.1] years) included in this IA full analysis set, 499 had lung, 387 breast, 192 colorectal and 212 ovarian cancer. Mean baseline Hb levels were <10 g/dL. At week 9, 426 (33%) patients had a Hb level of 10–12 g/dL, 165 (13%) of >12 g/dL, 226 (18%) of <10 g/dL and 473 (37%) had missing Hb values. 54% of the 672 patients still on the study at week 9 with available Hb values had Hb values of 10–12 g/dL. For patients with a baseline Hb of <10 g/dL, the Kaplan–Meier (K–M) percentage of patients with Hb levels ≥10 g/dL from week 1 to end of treatment period (EOTP) was 86%. For these patients, the K–M% of patients with Hb levels >13 g/dL from week 1 to EOTP was 10%. The K–M% of patients requiring RBC transfusions from week 5 to EOTP was 26% for all patients. Seven patients reported treatment-related non-serious adverse drug reactions, four were thromboses. Conclusions: This IA suggests most patients were treated according to European SmPC guidance. Hb evolution during the study is consistent with data from clinical trials, implying DA is effective in increasing Hb levels in chemotherapy-induced anaemia patients. Hb levels >13 g/dL were infrequent. Limitations are related to the observational nature of this study.

Darbepoetin alfa administration in patients with non-Hodgkin lymphoma and chemotherapy-induced anemia receiving (±R)CHOP

Abstract IMPACT NHL was a multicenter, observational study in adults with non-Hodgkin lymphoma receiving CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy with or without rituximab. Erythropoietin-stimulating agent treatment was given according to routine clinical practice and physician preference. In a subanalysis, outcomes were evaluated in 207 patients who received darbepoetin alfa (DA). The most common reason (81%) for initiating DA was low/declining hemoglobin (Hb) concentration. Mean (±standard deviation) duration of DA exposure was 8.8 ± 6.9 weeks (mean number of doses, 5.1 ± 4.6). Overall, 23% of patients had chemotherapy and DA treatment synchronized more than 75% of the time. At the time of DA initiation, 67% of patients had Hb concentrations in the guideline-recommended range (9–11 g/dl). Of 89 patients with Hb concentrations <10 g/dl at DA initiation and still receiving DA 5 weeks later, 92% (Kaplan–Meier) achieved Hb concentrations 10–12 g/dl between week 5 and at the end of treatment.

Analisi dei costi associati agli agenti stimolanti l’eritropoiesi nel trattamento dei pazienti con anemia indotta da chemioterapia in Italia

ObjectivesA cost analysis comparing darbepoetin-alfa (DARB), epoetin-alfa (EPO-A) and epoetin-beta (EPO-B) in the treatment of chemotherapy-induced anemia in Belgium concluded that costs of patients treated with DARB were significantly lower than costs of EPO-A- or EPO-B-treated patients. The objective of the present study was to adapt the Belgian analysis to the Italian setting, estimating differences in costs between erythropoiesis-stimulating agents (ESAs), considering ex-factory drug prices.MethodsThe absence of Italian longitudinal databases required to adapt the Belgian epidemiology and treatment pattern data to the Italian setting by adjusting the differences between countries. Belgian unit costs were replaced with the Italian ones. Italian ex-factory drug prices were used, and sensitivity analyses were performed using drug public prices. Costs were analyzed using a mixed-effects model stratified for propensity score quintiles.ResultsAfter finding similarities between the countries and adjusting for the Italian-specific setting, total management costs (including hospitalization, procedures, ESAs and other pharmaceutical costs) with DARB (Euro, year 2010) were €6,996 per patient, 24% and 19% lower than with EPO-A (p < 0.0001) and EPO-B (p = 0.0022), respectively. Anemia related costs (including hospitalization, procedures, ESAs and blood transfusion costs) with DARB were €1,786 per patient, 35% lower than with EPO-A (p < 0.0001). A statistically non-significant lower trend was shown when compared to EPO-B. Similar results were obtained with drug public prices.ConclusionsTotal and anaemia-related costs were lower in patients receiving DARB compared to those receiving EPO-A or EPO-B. These findings are consistent with those of the Belgian analysis, and confirm the economic efficiency of the administration of DARB in Italy.