Trajectory of Hemoglobin (Hb) in Patients Receiving Erythropoiesis-Stimulating Agents (ESAs) for Anemia Due to Concomitantly Administered Myelosuppressive Chemotherapy (CIA) (2006∼2008).

Anemia, a common hematologic complication of cancer and myelosuppressive chemotherapy, is often treated with ESAs, which include darbepoetin alfa (DA) and epoetin alfa (EA). Since 2007, the use of ESAs in CIA has been increasingly restricted in product labels, reimbursement, and practice guidelines. Prior analyses have indicated increasing transfusion rates over this period among CIA patients in the community setting. Little is known about the trajectory (or time path) of Hb levels prior to and after initiation of ESA therapy in real world practice. In particular, it is unknown whether recent ESA utilization restrictions have affected the change in Hb levels that chemotherapy patients experience prior to and after ESA initiation. This study analyzed Hb trajectories in CIA patients receiving ESAs from 2006 - 2008.

ESA episodes of care (ESA EOCs) within episodes of chemotherapy care (EOCCs) were identified from 2006 to 2008 in an oncology electronic medical records database of approximately 250,000 cancer patients receiving care from 111 practice sites across 25 states. An EOCC was identified by a gap of ≥90 days with no evidence of chemotherapy use. An ESA EOC was identified by a gap of ≥42 days without ESA therapy. To measure Hb trajectory over time, the difference between Hb at ESA initiation (baseline Hb) and mean Hb in each of the 6 weeks before and 6 weeks after ESA initiation was computed. Differences in means were compared by t-tests. Analysis of variance was done to test whether the differences differed by calendar year.

From 2006 to 2008, 22,357 ESA episodes were identified (EA: n=6,117, DA: n=16,420). Compared to 2006 (mean Hb=10.7 g/dL), ESAs were initiated at progressively lower baseline Hb levels overtime, 0.3 g/dL lower in 2007 (p<.001) and 1.0 g/dL lower in 2008 (p<.001). Average time from start of chemotherapy to initiation of ESA therapy increased from 44 days in 2006 to 66 days in 2008 (p<.001). Over the study period, mean Hb declined 1.3 g/dL in the 6 weeks prior to ESA initiation, and increased 0.7 g/dL in the 6 weeks after initiation. In the 6 weeks prior to ESA initiation, Hb decline was slightly different by calendar year (mean Hb decline 2006: 1.2 g/dL, 2007: 1.3 g/dL, 2008: 1.4 g/dL; p<0.050); in the 6 weeks after ESA initiation, Hb increase was not significantly different among the three years (mean Hb increase 2006: 0.7 g/dL, 2007: 0.7 g/dL, 2008: 0.8 g/dL; p=0.128).

In patients with CIA treated with ESAs between 2006 and 2008, Hbs at ESA initiation progressively declined likely in response to the changes in product labels, reimbursement and practice guidelines. There were no clinically significant differences in the rates of Hb changes observed from 2006 to 2008 before and after ESA initiation. Further research is needed to determine if earlier initiation of ESA therapy may help maintain Hb levels, improve patient's clinical outcomes and/or offset other health services such as the use of transfusions.

Hill: Amgen, Inc.: Research Funding. Cong: Amgen, Inc.: Employment. Hess: Amgen, Inc.: Research Funding. Nordyke: Amgen Inc.: Employment.