Comparison of the Management of Anemia in Patients with Solid Versus Hematological Malignancies Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from the European Anemia Cancer Treatment (A.C.T.) Study
Authors: Ludwig Heinz , Aapro Matti , Bokemeyer Carsten , Soubeyran Pierre , Muenzberg Michael , Turner Matthew , MacDonald Karen , Albrecht Tara , Abraham Ivo 
Published: April 2020

BACKGROUND. The A.C.T. study has shown that in Europe more cancer patients (pts) with anemia are being treated with ESAs than 7 years ago. ESAs are indicated in solid and hematological malignancies. Variability in treatment patterns, outcomes, and response rates in these tumor categories needs to be further explored.

OBJECTIVE. To examine differences in anemia treatment patterns, outcomes, and response rates between patients with solid vs. hematological malignancies.

DESIGN & PATIENTS. Multicenter, longitudinal retrospective study with 3 time points at approximately 1 month intervals; start of ESA treatment at visit 1. 307 centers in 13 European countries contributed 2192 pts (n=630 with hematological tumors; n=1562 with solid tumors) who were anemic (hemoglobin [Hb] 11g/dL) and treated with an ESA.

MEASUREMENTS. Retrospective chart review. Variables reported here: age, chemotherapy regimen, Hb, WHO/ECOG performance status, ESA type, ESA dose incl. escalation, and iron supplementation. Response to ESA Rx: Hb rise≥1g/dl within 8 weeks, hematopoietic response (Hb rise≥2g/dl or Hb≥12g/dl achieved), Hb rise≥2g/dl, and Hb target range of 12.0–12.9g/dl achieved by visit 3.

RESULTS. Pts ranged in age from 18 to 94 years (61.5 12.7) with no difference between groups (p=ns). 95.2% of pts were on chemotherapy, of which 92.9% on standard vs. 7.1% on high dose (solid 94.3% and 5.7% vs. hemato 89.1% and 10.9%, p=0.001); and 40.5% on platinum vs. 59.5% on nonplatinum (solid 49.1% and 50.9% vs. hemato 12.8% and 87.2%, p=&lt;0.001). Types of ESA included epoetin alfa (solid 23.2% vs. hemato 14.4%), epoetin beta (solid 41.7% vs. hemato 44.8%), darbepoetin alfa epoetin alfa (solid 34.6% vs. hemato 40.8%), and other epoetin alfa (solid 0.4% vs. hemato 0.0%; overall differences p&lt;0.001).

Table 1.

Visit 1 Visit 2 Visit 3 p p p Solid Hemato p Solid Hemato p Solid Hemato p (tumor type) (visit) (tumor type X visit) Mean (SD) ESA dose (IU/wk) 32601 (10037) 31067 (7247) &lt;0.001 33455 (11011) 32354 (9418) 0.034 33680 (11757) 32309 (9638) 0.027 0.023 &lt;0.001 n.s. Median ESAdose (IU/wk) 30000 30000 NA 30000 30000 NA 30000 30000 NA NA NA NA Mean (SD) Hb (g/dl) 9.6 (0.9) 9.3 (1.0) &lt;0.001 10.4 (1.2) 10.2 (1.5) 0.033 10.9 (1.4) 10.9 (1.7) n.s. 0.002 &lt;0.001 &lt;0.001 WHO/ECOG performance status 0.89 (0.73) 1.11 (0.87) &lt;0.001 0.77 (0.71) 0.92 (0.71) 0.002 0.76 (0.75) 0.88 (0.76) 0.013 &lt;0.001 &lt;0.001 0.004 % pts on iron 32.3% 16.5% &lt;0.001 22.6% 16.2% 0.006 22.4% 13.7% &lt;0.001 &lt;0.001 n.s. NA % pts on iron who are on IV iron 16.9% 24.5% n.s. 27.2% 34.5% n.s. 24.9% 32.7% n.s. n.s. n.s. NA % pts with &#x2028; ESA dose escalation 5.2% 6.5% n.s. 3.2% 2.5% n.s. n.s. n.s. NA

Table 2.

Hb ↑ ≥1g/dL Hb ↑ ≥1g/dL within 8 wks Hematopoietic response Hb ↑ ≥2g/dL Hb target 12–12.9g/dL Solid Hemato Solid Hemato Solid Hemato Solid Hemato Solid Hemato % of pts 63.0% 70.0% 53.4% 64.4% 35.5% 47.5% 29.8% 43.3% 17.9% 21.1% p 0.002 &lt;0.001 &lt;0.001 &lt;0.001 n.s.

CONCLUSIONS. Slight increase in mean ESA dose between tumor types and across visits was not in accordance with the stable median ESA dose. Hb increased from visit 1 from visit 3 for all pts, but more so for pts with hematological malignancy, who moreover started out at lower Hb levels. Performance status increased in parallel with Hb, but more so for hematological patients. Hb levels were found to be an interaction of tumor type and time. A concomitant pattern was observed for performance status. Iron supplementation with esp. IV iron was consistently low, however with more hematological pts receiving esp. IV iron. Dose escalation rates were low, perhaps reflecting that this be an individualized patient decision. Response rates for pts with hematological malignancies were consistently higher than those for solid tumors, except for reaching Hb target of 12–12.9 g/dl. Hematological pts tended to have ESA Rx initiated at lower Hb levels thus showing more room for Hb improvement and therefore greater likelihood to fall in various responder categories. Overall, an increase of 1g/dl is achievable for the majority of pts. Adding time constraints, increasing the threshold level to ≥2g/dl, and/or setting an evidence-based target range of 12–12.9g/dl is associated with lower response rates in both groups, with slight advantage for hematological patients within caution above. ESAs are effective and safe in the management of cancer-related anemia for pts with hematological malignancies and solid tumors.