Copenhagen, Denmark-Intravenous (IV) iron isomaltoside 1000 (Monofer) demonstrated sustained increases in hemoglobin (Hb) and fewer adverse events compared with oral iron sulphate in patients with chemotherapy-induced anemia (CIA), according to research presented by Gunnar Birgegard, MD, PhD, and colleagues at the 2015 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology Annual Meeting on Supportive Care in Cancer.
CIA is common in patients with cancer, and monotherapy with IV iron has been shown to correct cancer anemia. Dr Birgegard and colleagues conducted the PROFOUND study, comparing IV iron isomaltoside 1000 and oral iron sulphate monotherapy (ie, without erythropoiesis-stimulating agents [ESAs]) in patients with cancer with CIA.
The PROFOUND Study
"Cancer patients may have both true (absolute) and functional iron deficiency," explained Dr Birgegard, professor of hematology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. "IV iron improves the efficacy of ESA in cancer anemia."
PROFOUND was a phase 3, randomized, open-label, comparative, multicenter, 24-week, noninferiority trial conducted in a group of patients with nonmyeloid malignancies with anemia (Hb < 12 g/dL), serum ferritin < 800 µg/L, and transferrin saturation (TSAT) < 50%.
"TSAT below 50% actually means that we included both true iron deficiency and functional iron deficiency," Dr Birgegard explained. Only iron-restricted anemias and anemias of chronic disease were included in the study.
The primary end point was a change in Hb level from baseline to week 4. Secondary end points included changes in serum ferritin and TSAT, and tolerance. Demographic data and baseline biochemical differences, including Hb, TSAT, and ferritin, were comparable in the 2 groups.
IV and Oral Iron Doses Compared
After screening, 350 patients with CIA were randomized 2:1 to iron isomaltoside 1000 (n = 231) or oral iron sulphate (n = 119). Iron isomaltoside was administered to patients randomized 1:1 to infusion (n = 114) or injection (n = 117)
"The doses of iron were very different in the oral versus the IV group of course," said Dr Birgegard. The iron dose was calculated using a modified Ganzoni formula, with a target Hb of 13 g/dL, and an iron store of 500 mg.
The infusion group received single IV infusions of iron isomaltoside ≤1000 mg for 15 minutes weekly, and the injection group received repeated weekly IV bolus injections ≤500 mg over 2 minutes. The oral group received oral iron sulphate 200 mg daily for 12 weeks. The mean cumulative dose of IV iron was 849 mg, whereas the total oral iron dose was 13,539 mg.
IV Iron Better Tolerated Than Oral
The PROFOUND trial met the primary end point and showed noninferiority in increases in Hb from baseline at week 4 (mean change, IV iron 0.48 g/dL; oral iron, 0.44 g/dL; noninferiority test, P = .0002).
"The primary end point [change in Hb] was rather surprising to us because there was no significant difference between oral iron and IV iron," Dr Birgegard reported. "But there was a trend for faster Hb increase with IV iron during the first couple of weeks."
Patient responses to infusion and injection were the same, and a sustained effect on Hb was observed in both groups until week 24. In addition, patients with absolute iron deficiency (serum ferritin < 30 µg/L) responded better to both iron formulas.
Earlier and higher increases in TSAT were seen with IV iron, but no significant difference in Hb response was observed between patients with a TSAT < 20% versus a TSAT of 20% to 50%. However, there was a trend for a better response in patients with TSAT < 20% investigators reported.
IV iron was better tolerated than oral iron, and there was a low risk for serious reactions in both groups. More patients experienced an adverse drug reaction in the oral iron group compared with patients in the IV group (18.8% vs 6.6%; P <.0001).
Discontinuation was unusual in the IV group (0.9%) and more common in the oral group (8.9%). IV iron was well-tolerated as an infusion and bolus administration; no clinically significant hypophosphatemia events were reported.
"There has been a question of whether there is an issue with hypophosphatemia when giving IV iron, but there was no significant difference between IV iron and oral iron," Dr Birgegard stated. "All events were clinically insignificant."
At the end of the study, the investigators concluded that IV iron isomaltoside 1000 was better tolerated than oral iron, with significantly fewer adverse reactions and discontinuations.