Epoetin Alfa vs Best Standard of Care in Treatment of Anemia in Patients With Metastatic Breast Cancer Receiving Chemotherapy
Use of epoetin alfa (Epogen, Procrit) vs best standard of care to treat anemia did not achieve noninferiority for investigator-assessed progression-free survival in patients receiving chemotherapy for metastatic breast cancer, reported Leyland-Jones et al in the Journal of Clinical Oncology. Although noninferiority was achieved on independent review committee assessment of disease progression, red blood cell transfusion remains the preferred approach in this population.
Study Details
In this open-label trial, 2,098 women from 19 countries with a hemoglobin level ≤ 11.0 g/dL who were receiving first- or second-line chemotherapy for metastatic disease were randomized beginning in March 2006 to receive epoetin alfa at 40,000 IU subcutaneously once per week (n = 1,050) or best standard of care (n = 1,048). The primary endpoint was progression-free survival on investigator assessment.
For the epoetin alfa vs best standard of care groups, median age was 52 years in both, 66% vs 69% were white, 55% and 57% were postmenopausal, 80% vs 79% were receiving first-line chemotherapy, receptor status was hormone receptor–positive/HER2-negative in 43% vs 41%, HER2-positive in 39% in both, and triple-negative in 19% vs 20%. In addition, for the epoetin alfa vs best standard of care groups, 72% vs 71% had prior surgery, 81% in both had prior chemotherapy, 5% vs 4% had prior trastuzumab (Herceptin), 43% vs 40% had prior radiotherapy, and 36% vs 34% had prior hormonal therapy.
Progression-Free Survival
Median progression-free survival on investigator assessment was 7.4 months in the epoetin alfa group vs 7.4 months in the control group; the hazard ratio (HR) was 1.089, with a 95% confidence interval (CI) of 0.988 to 1.200, with the upper bound exceeding the prespecified noninferiority margin of 1.15. Median progression-free survival on independent review committee assessment was 7.6 months in both groups; the hazard ratio was 1.028, with a 95% CI of 0.922 to 1.146, with the upper bound thus not exceeding the prespecified noninferiority margin.
At the time of clinical cutoff, median overall survival was 17.2 months vs 17.4 months (HR = 1.057, 95% CI = 0.949–1.177), median time to tumor progression was 7.5 vs 7.5 months (HR = 1.094, 95% CI = 0.991–1.209), and overall response rate was 50% vs 51% (odds ratio = 0.950, 95% CI = 0.799–1.130).
Red blood cell transfusion was required in 5.8% of the epoetin alfa group vs 11.4% of the control group (P < .001). Thrombotic vascular events occurred in 2.8% vs 1.4% (P = .038).
The investigators concluded: “The primary end point, [progression-free survival] based on investigator-determined [disease progression], did not meet noninferiority criteria. As a consistency assessment with the primary finding, [progression-free survival] based on independent review committee–determined [disease progression] met noninferiority criteria. Overall, this study did not achieve noninferiority objective in ruling out a 15% increased risk in [disease progression]/death. [Red blood cell] transfusion should be the preferred approach for the management of anemia in this population.”
Janssen Research & Development supported this study.
Brian Leyland-Jones, MBBS, PhD, of Avera Cancer Institute, Sioux Falls, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
