San Antonio, TX—Adding an erythropoiesis-stimulating agent (ESA) to best supportive care failed to demonstrate noninferiority for progression-free survival (PFS) compared with best supportive care alone in patients with metastatic breast cancer, in a clinical trial known as EPO-ANE-3010 that was requested by the FDA.
Standard care alone or in combination with epoetin alfa (Epogen; Procrit) resulted in a median PFS of 7.4 months, as defined by investigator-assessed progressive disease. A separate analysis based on independent review showed identical PFS of 7.6 months in the 2 treatment groups. Moreover, investigator-determined time to progression showed a troubling increase in the risk for disease progression in patients who received the ESA.
The findings bring to full circle the use of ESAs for the treatment of chemotherapy-induced anemia, which has gone from enthusiastic support to disappointment, said Brian Leyland-Jones, MD, PhD, a medical oncologist at the Avera Cancer Institute, Sioux Falls, SD, who presented the trial results at the 2014 San Antonio Breast Cancer Symposium.
“For the management of anemia in the first- or second-line chemotherapy treatment of metastatic breast cancer, transfusion would be the preferred approach,” said Dr Leyland-Jones. “If epoetin alfa is to be used in the more advanced settings of metastatic breast cancer, this should be done very cautiously, in limited circumstances, only after a careful assessment of risks and benefits for epoetin alfa and alternative treatments—transfusion, interruption or cessation of chemotherapy—and with the patient fully involved in the decision-making process.”
An ongoing randomized, phase 3 clinical trial of darbepoetin alpha (Aransep) versus best supportive care for anemia in platinum-treated non–small-cell lung cancer is expected to provide additional information about the benefit-risk profile of ESAs, Dr Leyland-Jones added.
For more than a decade, concern has surrounded the use of ESAs in chemotherapy-related anemia. Two earlier studies of ESAs in metastatic breast cancer showed higher on-study mortality, no difference in time to progression, and a higher incidence of thrombotic events in patients who received ESAs. In 2004, the US Food and Drug Administration requested a trial to confirm findings from the EPO-INT-76 trial, which showed a 37% increased risk for on-study mortality in patients with metastatic breast cancer who received epoetin alfa but no difference in time to progression.
A principal investigator in the EPO-INT-76 trial, Dr Leyland-Jones presented the results from the new EPO-ANE-3010 trial, which was conducted at sites in 19 countries and enrolled 2098 patients receiving first- or second-line chemotherapy for metastatic breast cancer and a hemoglobin level of ≤11 g/dL.
The patients’ median age was 52 years; 25% of the patients had a body mass index of ≥30; 55% were postmenopausal; and the median hemoglobin level was 10.4 to 10.5 g/dL. Patients received a median of 8 doses of epoetin alfa, and the median weekly dose was 32,316.7 IU.
The overall survival was 17.2 months with epoetin alfa and 17.4 months with standard of care, a difference that did not meet criteria for noninferiority. The adverse event profiles were similar in the 2 treatment groups.
These results further question the use of ESAs in the treatment of anemia associated with chemotherapy.