Epoetin alfa missed its safety endpoint in metastatic breast cancer

FROM THE JOURNAL OF CLINICAL ONCOLOGY

A randomized phase III trial failed to allay safety concerns about the use of erythropoietin-stimulating agents in cancer patients, researchers reported online Feb. 8 in the Journal of Clinical Oncology.

The analysis could not rule out a 15% increase in the risk of progressive disease or death when women with metastatic breast cancer received epoetin alfa (EPO) instead of best standard of care for anemia, said Dr. Brian Leyland-Jones of Avera Cancer Institute in Sioux Falls, S.D., and his associates. Red blood cell transfusions should remain the preferred treatment for anemia in these patients, and any use of epoetin alfa for advanced cases “should be done with caution and based on careful risk-benefit assessment,” the researchers said.

Erythropoietin-stimulating agents can effectively treat cancer-associated anemia but have been linked to worse survival and locoregional control. However, the agents were used off label in several of these trials, the researchers noted. Therefore, they studied 2,098 women undergoing first- or second-line chemotherapy for metastatic breast cancer who had less than 11 mg/dL hemoglobin, an ECOG performance status of 0 or 1, and a life expectancy of at least 6 months. They randomly assigned patients to receive either standard treatment or 40,000 IU EPO once weekly until disease progression or the end of chemotherapy (J Clin Onc. 2016 Feb 8. doi: 10.1200/JCO.2015.63.5649 ). Median progression-free survival (PFS) was 7.4 months in both groups, but the EPO group was 9% more likely to die or develop progressive disease during the study, and the upper bound of the hazard ratio exceeded the prespecified noninferiority margin of 1.15 (hazard ratio, 1.089; 95% confidence interval, 0.988-1.200). An independent review committee calculated a median PFS of 7.6 months for both groups, and a hazard ratio whose upper bound fell just within the prespecified noninferiority margin (1.146). The EPO group needed about half as many red blood cell transfusions as did the control group (P less than .001), but experienced twice as many thrombotic vascular events (2.8% vs. 1.4%; P = .04).

“The results of this study do not suggest any new safety signal associated with EPO treatment and are consistent with the known safety risk to patients,” the researchers concluded. An ongoing randomized phase III study comparing darbepoetin with best standard of care for anemia in patients undergoing 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,” they said.

tor@frontlinemedcom.com

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