HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

No abstract

NCT00433927 (ClinicalTrials.gov); AIO KRK0306 FIRE-3.

Background and Aim: The role of IV iron supplementation during treatment with erythropoiesis-stimulating agents (ESAs) in patients with CIA is of increasing interest as a possible means of improving response. This randomized, open-label, multicenter study was designed to evaluate the safety and efficacy of IV iron vs standard practice in CIA patients receiving darbepoetin alfa. Interim efficacy analyses showed a higher response rate for darbepoetin alfa with IV iron compared to darbepoetin alfa with standard iron practice with no difference in the safety profile between the treatment arms (Vanderbroek et al, EHA 2006). Iron parameters are reported here. Methods: Eligible patients were diagnosed with a non-myeloid malignancy and had CIA with a baseline hemoglobin (Hb) value < 11g/dL. All patients received darbepoetin alfa 500 mcg administered Q3W with the SureClick™ prefilled autoinjector. Patients were randomized 1:1 to IV iron 200 mg (single dose Q3W at the same time as darbepoetin alfa or in 2 doses of 100 mg within 3 weeks) or standard practice (oral iron or no iron). Randomization was stratified by tumor type and baseline Hb category (< 10 or ≥10 g/dL). Results: A total of 400 patients were randomized. Mean (SD) age of the study population was 61.4 (11.5) years; range, 20–86. Sixty percent (n=241) of participants were women; 28% (n=114) had lung or gynecological tumors; and 52% (n=208) had a baseline Hb value ≥10 g/dL. In the interim analysis population (n=196), the mean (SD) weekly dose of IV iron was 64.8 (6.6) mg in the IV iron group (n=100). In the standard practice group, 28 of 96 patients (29%) received oral iron and 2 (2%) received IV iron (these patients were analyzed as randomized). Mean (standard error) serum ferritin concentrations and percent transferrin saturation (TSAT) in the 2 groups from baseline (BL) to end of study (EOS) are shown in the figure. Conclusions: The combination of darbepoetin alfa Q3W and IV iron appeared to be associated with a trend toward increased mean serum ferritin levels compared to the standard practice control arm. In contrast, mean TSAT surprisingly appeared to be similar in the 2 groups for most of the study period, perhaps suggesting that TSAT is influenced by other factors. Iron management appears to be an important factor in the response to ESAs and the findings presented here suggest the need for additional exploration into iron uptake and demand in cancer patients treated with darbepoetin alfa. Serum Ferritin Concentration Serum Ferritin Concentration Transferrin Saturation (%) Transferrin Saturation (%)

The study was designed to evaluate efficacy and superiority of capecitabine/bevacizumab + vinorelbine (CAP/BEV/VIN) compared to CAP/BEV alone. Main purpose was to introduce a taxane-/anthracycline-free first-line treatment in advanced breast cancer (ABC), in order to avoid long-term toxicities. In this open-label, superiority, phase 3 trial, patients with HER2-negative ABC were randomized 1:1 to receive either oral CAP at 1000 mg/m2 [twice daily, days 1–14, q3w] plus intravenous BEV at 15 mg/kg [day 1, q3w] (arm A) or in addition to this protocol intravenous VIN at 25 mg/m2 [days 1 + 8, q3w] (arm B) until disease progression, unacceptable toxicity or withdrawal of consent. Between 26 February 2009 and 26 October 2012, we randomised 600 patients (arm A N = 300; arm B N = 300) from 57 German outpatient-centres and 2 university hospitals. Median progression-free survival (PFS) (primary endpoint) was not improved with VIN (CAP/BEV, 8.8 months; CAP/BEV/VIN, 9.6 months; HR 0.84 [95 % CI 0.70–1.01], P = 0.058). Median overall survival (OS) (secondary endpoint) was 25.1 and 27.2 months for CAP/BEV and CAP/BEV/VIN, respectively, average HR 0.85 [95 % CI 0.70–1.03], P = 0.104). The 1- and 2-year OS rates appeared to be similar (78.0 and 77.0 %; 53.0 and 54.0 %). Toxicity profiles were generally mild and manageable. Adverse events occurred more frequently in arm B. Regarding the balance between clinical efficacy (PFS, OS) and toxicity, the CAP/BEV combination provides a favourable treatment option in first-line ABC avoiding taxane- and/or anthracycline-induced long-term toxicity. Superiority of CAP/BEV/VIN was not met, and side effects were even enhanced. Nevertheless, no safety issues occurred.