Use of iron sucrose and red blood cell transfusions in anaemic cancer patients in France (OncoFer study).

PURPOSE: This report describes the results of an observational, retrospective cohort study, evaluating the use of iron sucrose (IS) and red blood cell (RBC) transfusions in patients with cancer in routine clinical practice in France. A parallel investigated cohort treated with ferric carboxymaltose (FCM) has been reported earlier. METHODS: Data of patients with a solid tumour or haematological malignancy who have received IS or an RBC transfusion during 2010 from 3 months prior (M-3) to 3 months post first treatment (M+3) were analysed. RESULTS: Data from 46 patients who had received IS (400 mg median total iron dose) and 357 patients who had received RBC transfusions as first treatment (baseline) were included. Median haemoglobin levels improved from 9.9 g/dL (interquartile range 9.2; 11.0 g/dL) at baseline to 12.4 g/dL (11.4; 13.1 g/dL) at M+3 in IS-treated patients and from 8.2 g/dL (7.8; 8.8 g/dL) at baseline to 10.1 g/dL (8.8; 11.1 g/dL) in transfused patients. An erythropoiesis-stimulating agent was given to 54.3 and 28.9% of patients in the IS and the RBC transfusion groups, respectively, resulting in slightly better mean haemoglobin increase in both groups (2.4 vs 1.5 g/dL and 2.0 vs 1.6 g/dL, respectively). No severe nor serious adverse reaction and no hypersensitivity reactions were reported. CONCLUSION: Both IS and RBC transfusions effectively increased Hb levels in patients with cancer. IS was safe and well tolerated in this population. Considering prior reported results with FCM, using FCM may reduce ESA dose requirements and the required number of infusions.

Clinical use of ferric carboxymaltose in patients with solid tumours or haematological malignancies in France.

PURPOSE: This study collected data on the use of ferric carboxymaltose (FCM) in a cancer patient population in France to evaluate the feasibility and the conditions of use of FCM in routine clinical practice beyond the limiting criteria of clinical trials. METHODS: This observational, prospective study of patients with a solid tumour or a haematological malignancy who have received treatment with FCM after 01 July 2011 evaluated data about the circumstances of iron administration, concomitant medication and laboratory tests in the period from 3 months prior to the first FCM administration (baseline) until 3 months post-baseline. RESULTS: Data from 367 FCM-treated patients were analysed. FCM was mainly given as a single dose at baseline (69.2%) and without additional erythropoiesis-stimulating agent (ESA, 64.3%). The median total iron dose was 1000 mg per patient. Median haemoglobin (Hb) levels of FCM-treated patients improved from 10.3 g/dL (interquartile range 9.5, 11.1 g/dL) at baseline to 11.8 g/dL (11.1, 13.0 g/dL) until the end of the 3-month observational period. Patients treated with FCM alone or additional ESA achieved similar median Hb increase (1.3 [0.4, 2.1] g/dL and 1.4 [0.4, 2.5] g/dL, respectively). Patients with baseline Hb up to 11.0 g/dL and serum ferritin up to 500 ng/mL and beyond achieved stable median Hb levels ≥11.0 g/dL without signs of iron overload. No severe or serious adverse reaction and no hypersensitivity reactions were reported. CONCLUSIONS: The results of this observational study confirm the effectiveness and tolerability of FCM when given in clinical routine practice alone or in combination with an ESA.

Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: results from the 24-month follow-up of the BELA trial.

Bosutinib is an oral, dual SRC/ABL1 tyrosine kinase inhibitor for resistant/intolerant chronic myeloid leukaemia (CML). We assessed the efficacy and safety of bosutinib 500 mg/d (n = 250) versus imatinib 400 mg/d (n = 252) after >24 months from accrual completion in newly diagnosed chronic phase (CP)-CML (Bosutinib Efficacy and Safety in Newly Diagnosed CML trial [BELA]). Cumulative complete cytogenetic response (CCyR) rates by 24 months were similar (bosutinib, 79%; imatinib, 80%); cumulative major molecular response (MMR) rates were 59% for bosutinib and 49% for imatinib. Responses were durable; 151/197 vs. 172/204 and 125/153 vs. 117/131 responders remained on treatment and maintained CCyR and MMR, respectively. Since the 12-month primary analysis, no new accelerated-/blast-phase transformations occurred with bosutinib; four occurred with imatinib. Early response (BCR-ABL1/ABL1 ≤ 10%, 3 months) was associated with better CCyR and MMR rates by 12 and 24 months (both arms). Gastrointestinal events and liver function test elevations were more common, and neutropenia, musculoskeletal events and oedema were less common with bosutinib. Discontinuations due to adverse events were more common with bosutinib versus imatinib (most commonly alanine aminotransferase elevation: 4% vs. <1%); most occurred within the first 12 months. Cardiovascular adverse events were similar in both arms. Bosutinib continues to demonstrate good efficacy and manageable tolerability in newly diagnosed CP-CML patients.

Bosutinib in combination with the aromatase inhibitor exemestane: a phase II trial in postmenopausal women with previously treated locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer.

BACKGROUND: Bosutinib is an oral, selective Src/Abl tyrosine kinase inhibitor with activity in breast cancer (BC). We evaluated bosutinib plus exemestane as second-line therapy in previously treated hormone receptor-positive (HR+) locally advanced or metastatic BC. METHODS: This was a phase II study with patients enrolled in a single-arm safety lead-in phase. Patients receiving bosutinib at 400 mg or 300 mg/day (based on toxicity) plus exemestane at 25 mg/day were monitored for adverse events (AEs) and dose-limiting toxicities for 28 days, and initial efficacy was assessed. After the lead-in and dose-determination phase, randomized evaluation of combination therapy versus exemestane was planned. RESULTS: Thirty-nine of 42 patients (93%) experienced treatment-related AEs including diarrhea in 28 (67%) and hepatotoxicity in 11 (26%); overall serious treatment-related AEs were recorded in 4 (10%). No liver toxicity met Hy's law criteria. Dose-limiting toxicities occurred in 5 of 13 patients receiving 400 mg (38%) and 3 of 26 patients receiving 300 mg (12%) of bosutinib; all resolved on treatment discontinuation. One patient (300 mg/day) achieved confirmed partial response; three (400 mg/day, n = 2; 300 mg/day, n = 1) maintained stable disease for >24 weeks; a best response of progressive disease occurred in 15 of 42 patients (36%). Median progression-free survival was 12.3 weeks (80% confidence interval: 11.0-15.6). CONCLUSION: The risk-benefit profile of bosutinib at 300 mg/day plus exemestane resulted in early study termination before the randomized portion. Alternative bosutinib regimens merit investigation in BC.

Bosutinib in combination with the aromatase inhibitor letrozole: a phase II trial in postmenopausal women evaluating first-line endocrine therapy in locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer.

BACKGROUND: Endocrine therapy resistance in hormone receptor-positive (HR+) breast cancer (BC) may involve crosstalk between HRs and growth factor signaling pathways. We evaluated bosutinib, a dual Src/Abl tyrosine kinase inhibitor that has previously demonstrated some antitumor activity in BC, plus letrozole as first-line endocrine therapy in locally advanced or metastatic HR+/HER2- BC. METHODS; Sixteen postmenopausal women were enrolled in a phase II study evaluating the safety/efficacy of bosutinib plus letrozole. In the single-arm safety/dose-confirming lead-in (part 1), patients received oral bosutinib at 400 mg/day plus letrozole at 2.5 mg/day; adverse events (AEs) and dose-limiting toxicities (DLTs) were monitored, and initial efficacy was assessed. A randomized efficacy/safety phase (part 2) was planned to evaluate the combination versus letrozole monotherapy. RESULTS: Fifteen of 16 subjects experienced treatment-related AEs, most commonly diarrhea (69%). Treatment-related hepatotoxicity AEs (primarily alanine aminotransferase [ALT] or aspartate aminotransferase [AST] elevations) occurred in 6 of 16 patients (38%). Four of 15 evaluable patients (27%) experienced a DLT (grade 3/4 ALT/AST elevations, n = 2; grade 3 rash, n = 1; grade 3 diarrhea or vomiting, n = 1), including 1 Hy's law hepatotoxicity case. All DLTs resolved following treatment discontinuation. One patient achieved confirmed partial response; one had stable disease for >24 weeks. Study termination occurred before part 2. CONCLUSION: The unfavorable risk-benefit ratio did not warrant further investigation of bosutinib plus letrozole.

Safety of bosutinib versus imatinib in the phase 3 BELA trial in newly diagnosed chronic phase chronic myeloid leukemia.

Bosutinib, an orally active, Src/Abl tyrosine kinase inhibitor, has demonstrated clinical activity and acceptable tolerability in chronic phase chronic myeloid leukemia (CP CML). This updated analysis of the BELA trial assessed the safety profile and management of toxicities of bosutinib versus imatinib in adults with newly diagnosed (≤6 months) CP CML after >30 months from accrual completion. Among patients randomized to bosutinib 500 mg/d (n = 250) or imatinib 400 mg/d (n = 252), 248 and 251, respectively, received ≥1 dose of study treatment. Adverse events (AEs; any grade) with bosutinib versus imatinib were significantly more common for certain gastrointestinal events (diarrhea, 70% vs. 26%; P < 0.001; vomiting, 33% vs. 16%; P < 0.001), alanine aminotransferase (33% vs. 9%; P < 0.001) and aspartate aminotransferase (28% vs. 10%; P < 0.001) elevations, and pyrexia (19% vs. 12%; P = 0.046). AEs significantly less common with bosutinib included edema (periorbital, 2% vs. 14%; P < 0.001; peripheral, 5% vs. 12%; P = 0.006), musculoskeletal (myalgia, 5% vs. 12%; P = 0.010; muscle cramps, 5% vs. 22%; P < 0.001; bone pain, 4% vs. 11%; P = 0.003), increased creatine phosphokinase (8% vs. 20%; P < 0.001), neutropenia (13% vs. 30%; P < 0.001), and leukopenia (9% vs. 22%; P < 0.001). Between-group differences in the incidence of cardiac and vascular AEs were not significant. Diarrhea was typically transient, mostly Grade 1/2, occurring early during treatment, and was manageable with antidiarrheal medication. Despite higher rates of aminotransferase elevation with bosutinib, events were managed in most patients with dose modification and/or concomitant medication. Bosutinib had a manageable safety profile distinct from that of imatinib in patients with newly diagnosed CP CML.

High prevalence of iron deficiency in patients with acute decompensated heart failure.

AIMS: Limited data are available on iron parameters in patients hospitalized for decompensation of chronic heart failure. METHODS AND RESULTS: Iron parameters of patients hospitalized for decompensation of chronic heart failure were prospectively assessed during the 72 h after hospital admission. Iron deficiency was defined according to the 2012 European Society of Cardiology Guidelines. Overall, 411 men (75 ± 12 years; 75% NYHA functional classes III/IV) and 421 women (81 ± 11 years; 71% NYHA classes III/IV) were evaluated. The prevalence of iron deficiency was 69% in men and 75% in women (including 41% and 49% with absolute iron deficiency, respectively). The prevalence of anaemia in men (<13 g/dL) was 68% and in women (<12 g/dL) it was 52%. Among non-anaemic patients, the prevalence of iron deficiency was 57% in men and 79% in women. Only 9% of patients received iron supplementation at the time of admission (oral, 9%; intravenous, 0.2%). Multivariate analysis showed that anaemia and antiplatelet treatment in men, and diabetes and low C-reactive protein in women, were independently associated with iron deficiency. CONCLUSIONS: Iron deficiency is very common in patients admitted for acute decompensated heart failure, even among non-anaemic patients. Given the benefit of iron therapy in chronic heart failure, our results emphasize the need to assess iron status not only in chronic heart failure patients, but even more so in those admitted for worsening heart failure, regardless of gender, heart failure severity, or haemoglobin level. Initiating iron therapy in hospitalized heart failure patients needs to be investigated.