EPO Fails Non-Inferiority Test For Anaemia Care During Metastatic Breast Cancer Chemotherapy

Epoetin alfa does not meet all non-inferiority survival criteria compared with the best standard of care for anaemic patients receiving metastatic breast cancer chemotherapy

medwireNews: Red blood cell (RBC) transfusion is the optimal means of managing anaemia in women undergoing chemotherapy for metastatic breast cancer, suggest researchers in the Journal of Clinical Oncology.

Epoetin alfa (EPO) 40,000 IU per week did not meet all non-inferiority criteria ruling out a 15% increase in the risk of progressive disease or death compared with the best standard of care for patients with a haemoglobin level of 11.0 g/dL or lower during first- or second-line chemotherapy based on established guidelines, such as the National Comprehensive Cancer Network.

All patients had at least one measurable metastatic lesion, a life expectancy of greater than 6 months and an ECOG performance status of 0 or 1.

The primary endpoint of median progression-free survival (PFS) in the open-label trial of 2098 patients was 7.4 months in both treatment groups, when determined by the trial investigators, giving a hazard ratio (HR) of 1.089. The upper bound of the 95% confidence interval was 1.200, which exceeded the prespecified noninferiority margin of 1.15.

When calculated by an independent review committee, the median PFS was 7.6 months in both groups and the HR was 1.028. But the upper bound of the 95% confidence interval did not exceed the predefined noninferiority margin in this analysis, thus ruling out a 15% increase in the risk of death or progression in EPO users.

At clinical cutoff after 1337 deaths, overall survival was a comparable median of 17.2 months for the EPO-treated patients and 17.4 months for those who received best standard of care.

The median investigator-determined time to tumour progression was 7.5 months for both groups, whereas the independent review committee gave a median time of 8.0 and 8.3 months for the EPO and best standard of care groups, respectively.

Patients who received EPO were significantly less likely to require red blood cell transfusion than those given the best standard of care (5.8 vs 11.4%) but significantly more likely to experience vascular thrombosis (2.8 vs 1.4%).

“In light of these study results, RBC transfusion should be the preferred approach for the management of anemia during first- or second-line chemotherapy for metastatic breast cancer”, say Brian Leyland-Jones, from Avera Cancer Institute in Sioux Falls, South Dakota, USA, and co-authors.

While the researchers did not detect any novel safety signals associated with EPO, they suggest it should be used “with caution” in advanced breast cancer patients, “based on careful risk-benefit assessment”.

The investigators add: “The ongoing randomized phase III study of darbepoetin versus BSC (NT00858364; Anemia Treatment for Advanced Non-Small Cell Lung Cancer [NSCLC] Patients Receiving Chemotherapy), for anemia secondary to platinum-based treatment of stage IV non–small-cell lung cancer, will further inform the benefit-risk profile of [erythropoietin-stimulating agents] in the oncology setting.”


Leyland-Jones B, Bondarenko I, Nemsadze G, et al. A randomized, open-label, multicenter, phase III study of epoetin alfa versus best standard of care in anemic patients with metastatic breast cancer receiving standard chemotherapy. J Clin Oncol 2016; Advance online publication 8 February. doi: 10.1200/JCO.2015.63.5649

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