Ten years of meta-analyses on erythropoiesis-stimulating agents in cancer patients.

BACKGROUND:

Since erythropoiesis-stimulating agents (ESAs) were licensed in 1993, more than 70 randomized controlled trials and more than 20 meta-analyses and systematic reviews on their effectiveness were conducted. Here, we present a systematic review on the meta-analyses of trials evaluating ESAs in cancer patients.

METHODS:

We included all published meta-analyses of at least five randomized controlled trials that evaluated the effects of ESAs versus control in patients with any type of cancer or myelodysplastic syndrome.

RESULTS:

We included a total of 23 systematic reviews and meta-analyses (16 literature based and 7 based on individual patient data (IPD)) that assessed several outcomes. All 12 meta-analyses reporting on transfusion risks demonstrated that ESAs significantly reduce the risk of transfusions. Eleven meta-analyses (nine based on published data and two on IPD) evaluated thrombovascular events. An increased risk of thrombovascular events was observed in all but two meta-analyses (relative risks (RRs) ranging from 1.57 to 1.69). However, potential reporting and publication bias as well as detection bias call for a cautious interpretation of these results. Survival and mortality were evaluated in 18 meta-analyses, with the observed effect changing over time. While meta-analyses on studies conducted before 2002 showed beneficial effects of ESAs on survival, contrary results, i.e. worsened survival, was seen in meta-analyses including more recent studies.

DISCUSSION:

The results from several meta-analyses show that ESAs in cancer patients reduce the risk for red blood cell transfusions and increase the risk for thrombovascular events and mortality. The effect of ESAs on mortality risk in patients receiving chemotherapy remains unclear. In clinical practice, the benefits and risks of ESAs should be carefully considered and decisions should be made based on each patient's situation and preferences.