Epoetin Alfa Biosimilar Treatment for Chemotherapy-Induced Anemia in Current Oncology and Hematology Practice: An Iron Supplementation Subanalysis of the Synergy Study

Background

Recommendations on erythropoiesis-stimulating agents (ESAs) for the management of chemotherapy-induced anemia (CIA) are well established (Schrijvers D et al. Ann Oncol 2010;21[suppl 5]:v244–7). Iron supplementation can further improve treatment response of CIA, particularly in the case of iron deficiency (Pedrazzoli P et al. J Clin Oncol 2008;26:1619–25; Auerbach M et al. J Clin Oncol 2004;22:1301–7), but is under-used.

Objective

To evaluate the effect of epoetin alfa biosimilar, with or without iron, on CIA in current oncology and hematology practice.

Methods

SYNERGY was an observational, longitudinal, prospective, multicenter study conducted in France, from a representative, random sample of oncologists and hematologists. Patients of these clinicians were aged ≥18 years with solid tumors, lymphoma and/or myeloma and CIA, eligible for treatment with epoetin alfa biosimilar and followed for 12–16 weeks. A subanalysis describing the treatment response to epoetin alfa biosimilar in patients with/without iron supplementation and their target hemoglobin (Hb) levels is presented here.

Results

Overall, 2167 patients were enrolled by 195 French oncologists/hematologists during June 2012–December 2014. The analysis included 2076 patients, of whom half were male. At inclusion, mean age ± standard deviation (SD) was 67±12 years and 75.7% (n=1517) of patients had a World Health Organization performance status of 0 or 1. Most patients had not received any blood transfusions (90.0%, n=1867) or ESAs (93.1%, n=1932) in the year before the inclusion visit. A total of 31.6% (n=655) patients received iron supplementation, of whom 58.9% (n=386) received intravenous (IV) iron, 40.5% (n=265) had oral iron and 0.6% (n=4) were prescribed both oral and IV iron. An iron status assessment was more common in patients who were given iron supplementation, while over a third of patients who did not have an iron status were prescribed iron (Table). At follow-up, over 70% of patients had a maximum Hb level above 11 g/dL, regardless of iron status (Table). For patients with and without added iron, the mean change in Hb level was 2.26 g/dL and 2.22 g/dL at maximum during the study and 1.71±1.52 g/dL and 1.59±1.60 g/dL at final visit, respectively.

Iron status results were used to define patients as having absolute iron deficiency (coefficient of saturation of transferrin [CST] <20% and ferritin <100 μg/100 mL), functional iron deficiency (CST <20% and ferritin ≥100 µg/100 mL) or no deficiency (CST ≥20%). The majority of patients with no iron supplementation had no deficiency compared with a minority of patients with iron supplementation (Table). Patients with absolute iron deficiency given iron supplementation responded better to epoetin alfa biosimilar (increase of ≥1 g/dL since enrollment or increase of ≥2 g/dL, in the absence of transfusion in the 3 previous weeks) than those not given iron supplementation (74.5% vs 65.5%, p=0.403). Similar results were observed for patients with added IV iron.

	Iron supplementation	No iron supplementation
Iron status assessed; n (%) No Yes	n=655 259 (39.5) 396 (60.5)	n=1421 743 (52.3) 678 (47.7)
Hb levels (g/dL) at inclusion; mean ± SD	n=655 9.57±0.7	n=1421 9.62±0.7
Maximum Hb value (g/dL) reached during study in patients who completed the study; n (%)	n=593	n=1280
≤9 g/dL	13 (2.2)	16 (1.3)
9–11 g/dL	157 (26.5)	340 (26.5)
≥11 g/dL	423 (71.4)	924 (72.2)
Maximum change in Hb value; mean g/dL ± SD, in patients who completed study	n=593 2.22±1.4	n=1280 2.26±1.4
Association of epoetin alfa biosimilar use* and iron deficiency; n (%)
Absolute iron deficiency	49 (62.0)	30 (38.0)
Functional iron deficiency	182 (56.5)	140 (43.5)
No iron deficiency	88 (18.6)	384 (81.4)
Responder to epoetin alfa biosimilar*; n (%)
Absolute iron deficiency	35 (74.5; p=0.403)	19 (65.5)
Functional iron deficiency	109 (68.1; p=0.958)	78 (67.8)
No iron deficiency	56 (69.1; p=0.489)	251 (73.0)

*During the first or second chemotherapy cycle after inclusion

Hb, hemoglobin; SD, standard deviation

Conclusions

Overall, these results provide real-life evidence that epoetin alfa biosimilar was effective in treating anemia. Iron supplementation improved the response to epoetin alfa biosimilar in patients with an absolute iron deficiency, suggesting that iron status can be used to optimize treatment of patients with CIA with ESAs and iron supplementation.