Epoetin-β treatment in patients with cancer chemotherapy-induced anaemia: the impact of initial haemoglobin and target haemoglobin levels on survival, tumour progression and thromboembolic events

Abstract

BACKGROUND: Epoetin-b is used to treat patients with cancer undergoing chemotherapy to alleviate the symptoms of anaemia, reduce the risk of blood transfusions and improve quality of life (QoL). METHODS: This meta-analysis of all 12 randomised, controlled studies of epoetin-b evaluated the impact of therapy at different Hb-initiation levels and to different target Hb levels on overall survival, tumour progression and thromboembolic events (TEE). An analysis of risk factors pre-disposing patients to TEEs under epoetin-b therapy was also performed. A total of 2297 patients are included in the analysis. RESULTS: Analyses based on various Hb-initiation levels indicate no detrimental impact on survival (HR 0.99; 95% CI 0.70, 1.40) and a favourable impact on disease progression (HR 0.73; 95% CI 0.57, 0.94) when epoetin-b was used within its licensed indication (Hb initiation p10 g dl À1 ) or the EORTC recommended level of 11 g dl À1 . An increased risk of TEEs is seen for all Hb-initiation level strata and a detrimental impact on survival is seen when initiating epoetin-b therapy at Hb levels 411 g dl À1 . We observe no association between high target Hb levels (X13 g dl À1 ) and an increased risk of mortality, disease progression or TEEs with epoetin-b compared with control. CONCLUSION: The results of this analysis indicate that epoetin-b therapy has no detrimental impact on survival or tumour progression when initiated at Hb levels up to 11 g dl À1 . Furthermore, there is no evidence to suggest that high Hb values achieved during epoetin-b therapy are associated with an increased mortality, disease progression or TEE rate.

Recombinant Human Erythropoietin in Combination with Chemotherapy Increases Breast Cancer Metastasis in Preclinical Mouse Models

“…In summary, there have been a large number of trials investigating ESAs for the treatment of CIA in cancer patients (5,(10)(11)(12)(13)(14)(15)32). In several trials, an increase in thrombotic events was seen in the ESA arm (6,8,11,54).…”

“…More importantly, meta-analyses show a decrease in overall survival in the ESA arm of some studies (6,8). This has prompted concern about the use of rHuEPO in cancer patients with anemia because, although the cause of this decreased survival is unknown, it has been speculated that the administration of rHuEPO may cause cancer progression (8,10). This preclinical study aimed to shed some light on the observed clinical effect of rHuEPO by investigating the expression and function of EPOR in preclinical model systems of human breast cancer metastasis.…”

“…2 of these published studies (BRAVE and BEST) have been limited to patients with metastatic disease (10,11). However, these studies contradict each other in their findings, with the BRAVE study detecting no difference in overall survival between treatment arms (10), whereas the BEST study was ended early because of a higher mortality rate in the rHuEPO-treated versus placebo arm (11).…”

“…There have been multiple trials evaluating the effect of ESAs on patients with breast cancer (5,(10)(11)(12)(13)(14)(15). Of these, 2 studies (BRAVE and BEST) included only patients with metastatic disease (10,11).…”

“…Of these, 2 studies (BRAVE and BEST) included only patients with metastatic disease (10,11). The BRAVE study evaluated a once weekly dose of rHuEPO and detected no difference in overall survival (10). The BEST study was ended early because of a higher mortality rate at 12 months in the rHuEPO-treated versus placebo arm (11).…”