Analysis of the effect of body weight on the efficacy and safety of epoetin alfa

Abstract

8184 Background: Epoetin alfa for cancer-associated anemia is effective given as a weight-based dose (WBD; 150 IU/kg) or fixed dose (FD; 10,000 IU) 3-times weekly (TIW), or a FD (40,000 IU) once weekly (QW). Methods: To evaluate the effect of body weight on efficacy of FD vs WBD epoetin alfa, data from a FD trial (40,000 IU QW increased to 60,000 IU QW for insufficient response; N = 2964; Gabrilove 2004) and data from 8 WBD studies (150 IU/kg TIW increased to 300 IU/kg for insufficient response; N = 944) were analyzed and compared. Body weights were defined by quartiles (Q) derived from the European Cancer Anaemia Survey (Ludwig 2004). Efficacy endpoints were erythropoietic response (ER; hemoglobin [Hb] increase ≥2 g/dL) and Hb change from baseline. Safety was evaluated across weight categories in the FD trial. Results: Heavier patients (Q4; >79.5 kg) in the FD group had significantly (P=.0182) lower ER than lighter patients (Q1; ≤60.3 kg), 61% vs 66%, respectively. In the WBD group ER for heavier- vs lighter-weight patients was 63% vs 76%, respectively (P=.0779). Difference in effect of body weight on ER between the dosing regimens was not significant (P=.3005). FD epoetin alfa was effective in 58% of patients >95.9 kg. Heavier patients had slightly less Hb increase from baseline with the FD (2.0 g/dL Q1, 1.8 g/dL Q4; NS) and WBD (2.3 g/dL Q1, 1.9 g/dL Q4; NS). Even for patients who weighed ≥95.9 kg, mean Hb change was >1.5 g/dL. Probability of dose increase with the FD was 28% in Q1 and 42% in Q4 (P<.0001) indicating that heavier patients were more likely to receive a dose increase, as suggested by the lower ER. Differences in dose increases with WBD were not significant, ranging between 25% and 35%. Safety of FD epoetin alfa was similar across all body-weight quartiles indicating that safety was not compromised in lower-weight patients. Conclusion: Epoetin alfa administered as a FD is effective, even in patients >95 kg, but WBD may be preferable in heavier weight patients. Tolerance is excellent regardless of body weight. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson Ortho-Biotech