A Prospective Observational Study Exploring the Impact of Iron Status On Response to Darbepoetin Alfa in Patients with Chemotherapy Induced Anemia.

Chemotherapy-induced anemia (CIA) is a complication of cancer therapy. Erythropoiesis Stimulating Agents (ESA) increase hemoglobin (Hb) concentration, if folate, vitamin B12 and iron levels are sufficient.

This multicenter, prospective observational study explored response to darbepoetin alfa (DA) (Aranesp^®) 500 μg Q3W or 300 μg Q2W in correlation with iron status in cancer patients with CIA. Secondary objectives were: safety and Hb outcome, Hb concentration at treatment initiation, and prescription behavior of physicians. All anemic patients foreseen to receive DA were enrolled in a registry. Data on baseline (BL) characteristics were collected. Subsequently, patients with normal vitamin B12 and folate were eligible for follow-up (FU).

481 adult cancer patients with CIA (defined as Hb <11 g/dL as per EORTC guidelines (2007) and DA label at time of recruitment), treated in 26 oncology and hematology centers in Belgium and Luxemburg between December 2006 and April 2008, were enrolled in the registry. Mean ±SD age was 63.7±11.5 years; 42.5% of patients were male. Most patients (87.5%) had a solid tumor, mainly NSCLC, breast and colorectal cancer, and 54.4% were metastatic. DA treatment was initiated before the 4^th cycle of chemotherapy in 82.5% of patients, planned to be synchronised with chemotherapy in 73.5% of patients and DA 500 μg Q3W was the most prescribed dose schedule (76.8%) in patients with solid and hematological tumors. Of the 481 enrolled subjects, 414 subjects were eligible for FU (396 subjects with available Hb data, and 379 subjects with available iron data). For patients with available Hb data (n=396), the mean ±SD Hb was 9.9±0.7 g/dL (range: 9.8-10) at inclusion and 10.9±1.7 g/dL (range: 10.7-11.1) at end of treatment. Hb target (≥11 g/dL) was reached by 87.4% (KM estimate; 95% CI: 81.2-92.3) of patients after a median time of 39.0 days (KM est.; 95%CI: 29.0-42.0). Iron deficiency was defined as having a Ferritin <100 ng/ml and/or TSAT <20% at inclusion or at any time on study. Of the 396 patients, 170 (42.9%) were iron deficient (ID) at inclusion. Hb target was achieved by 85.9% (KM est; 95%CI: 75.8-93.3) of patients with ID at inclusion vs 87.8% (KM est; 95%CI: 79.1-94.2) of patients without ID at inclusion. Among these iron deficient patients 20% received DA + iron. Hb target was reached more often (KM est: 100%) in these patients than in those not receiving iron treatment (KM est: 75.9%; 95% CI: 62.7-87.1) and the median time to target was also shorter (KM est: 28.5 days; 95% CI: 21.0-43.0) with iron than without (KM est: 42.0 days; 95% CI: 34.0-56.0). For patients with available iron FU data (n=379), the number of patients with ID at any time on study was 197 (52%). Thirty-six of these patients received DA + iron and reached Hb target after a median time of 28.5 days (KM est; 95% CI: 21.0-42.0) compared to 47.0 days (KM est; 95% CI: 35.0-62.0) for subjects not receiving iron. Among patients who were never iron-deficient during the study (101/379), 16 were given iron supplement and reached Hb target faster (KM est. median time: 21.0 days; 95% CI: 9.0-21.0, vs. 32.0 days; 95% CI: 21.0-55.0) than those not supplemented. The number of patients needing blood transfusion was similar regardless of iron deficiency at inclusion (KM est: 32.0% for ID vs. 35.5% for non ID). The DA treatment was safe: 5 patients reported moderate adverse drug reaction, none of them being serious.

DA administered to cancer patients with CIA increased their Hb levels. Iron supplementation in iron deficient patients improved DA effectiveness although additional investigation is needed to draw any firm conclusions.

Beguin:Amgen: Research Funding. Bosly:Amgen: Research Funding.