Investigation of Epoetin alfa (EPO) 80,000 Units (U) Every 4 Weeks (Q4W) vs. 40,000 U Every 2 Weeks (Q2W) in Patients with Cancer Not Receiving Chemotherapy (CT) or Radiation Therapy (RT): Final Results.

Recent investigational studies have explored the use of epoetin alfa for the treatment of cancer-related anemia in patients not receiving CT or RT. Previous studies in this patient population showed that EPO was effective in treating anemia at regimens of 40,000 U weekly, 60,000 U Q2W, and 80,000 U every 3 weeks. Because these patients do not experience the myelosuppressive effects of CT or RT, a lower cumulative dose of EPO may be efficacious. The current pilot study was designed to investigate two novel dosing regimens in this population. Based on recent safety concerns from studies with another ESA in cancer patients not receiving CT or RT, enrollment in this study was stopped prematurely. This prospective, randomized, open-label, multi-center study was to enroll 100 patients with an active non-myeloid malignancy, baseline (BL) hemoglobin (Hb) level ≤11 g/dL, and not receiving or planning to receive CT or RT during the course of the study. Non-cytotoxic antineoplastic therapy was allowed. Patients were randomized 1:1 to receive EPO subcutaneously either 80,000 U Q4W (maximum 13-week treatment period) or 40,000 U Q2W (maximum 15-week treatment period). Hb levels were obtained weekly in all patients. EPO was held for Hb level >13 g/dL; dose was reduced for Hb >12 g/dL or Hb increase >1 g/dL in any 2-week period. The primary efficacy endpoint was hematopoietic response (HR), defined as a ≥1 g/dL rise in Hb from BL. Enrollment was stopped at 60 patients (safety population; 29 Q4W, 31 Q2W). All received at least a partial planned cumulative dose of study drug. BL characteristics were similar: % female, 59% Q4W and 61% Q2W; mean age, 73 years Q4W and 71 years Q2W; ECOG 0–1 83% Q4W and 96% Q2W; mean BL Hb, 10.3 g/dL Q4W and 9.9 g/dL Q2W. Prostate was the most common tumor site in both the Q4W (n=6, 21%) and Q2W (n=10, 32%) groups. Efficacy was analyzed in 59 (28 Q4W, 31 Q2W) patients who also had at least one post-BL Hb value (mITT population). HR was achieved in 25 patients (89.3%; 95% CI 71.8, 97.7) in the Q4W group and 28 patients (90.3%; 95% CI 74.2, 98.0) in the Q2W group. The median time to achieve HR was 14 days in the Q4W group and 20 days in the Q2W group. Packed red blood cell transfusion rates for the period Day 29 through end of study were 10.7% (n=3) among Q4W patients and 3.2% (n=1) among Q2W patients. Fewer Q4W (n=20, 69%) vs. Q2W (n=27, 87%) patients required an EPO dose reduction or dose hold. Four patients in each group experienced a serious adverse event unrelated to study drug. No clinically relevant TVEs were reported among Q4W patients, while 2 events (myocardial ischemia and deep vein thrombosis) were reported in a single patient in the Q2W group. Two deaths (both attributed to disease progression) were reported in the Q2W treatment group. The two novel dosing regimens investigated in this study (80,000 U Q4W and 40,000 U Q2W) produced comparable efficacy (with approximately 90% response to either dose regimen) and safety outcomes. Although this study reinforces the dosing flexibility of epoetin alfa with dosing intervals of up to 4 weeks, current labeling warns against the use of ESAs in these types of patients with active malignant disease receiving neither CT or RT.