Effects of Funding Policy Changes and Health Warnings on the Use of Erythropoiesis-Stimulating Agents [Original Contributions]

Effects of Funding Policy Changes and Health Warnings on the Use of Erythropoiesis-Stimulating Agents [Original Contributions]

Purpose:
To characterize the effects of formulary changes and governmental safety warnings on use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.

Patients and Methods:
We conducted a cross-sectional time-series analysis using health administrative data from Ontario, Canada. From January 1997 to December 2009 we identified all ESA initiations among patients diagnosed with cancer. We explored the effects of two formulary changes that progressively liberalized coverage for ESAs, first by rescinding the requirement for blood transfusion in 2003 and then by removing all restrictions in 2007. We also explored the effect of US Food and Drug Administration and Health Canada warnings issued in the second quarter of 2007. To assess regional variability in ESA use, we determined prescription rates for each of Ontario's 14 regional cancer centers.

Results:
After the first formulary change, the ESA initiation rate increased to 1.66 new users per 1,000 patients with cancer, 374% more than predicted (P < .001). After the second formulary change, the initiation rate increased to 3.97 new users per 1,000 patients with cancer, 73% more than predicted (P < .001). After the safety warnings, this rate declined 81% by study end (P < .001). We found significant regional variation in ESA use.

Conclusion:
Formulary access and safety warnings had significant impacts on the new use of ESA drugs in patients with cancer. This suggests that both are effective means of influencing the use of these drugs. Variable ESA prescription rates across our region may reflect a lack of consensus regarding their utility.

open access: British Journal of Cancer - Effects of erythropoietin receptors and erythropoiesis-stimulating agents on disease progression in cancer (safety, adverse events, disease progression, conflicting research.....)

Blogger's Note: note ties to industry
          
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"Erythropoiesis-stimulating agents (ESAs) increase red blood cell (RBC) production in bone marrow by activating the erythropoietin receptor (EpoR) on erythrocytic-progenitor cells. Erythropoiesis-stimulating agents are approved in the United States and Europe for treating anaemia in cancer patients receiving chemotherapy based on randomised, placebo-controlled trials showing that ESAs reduce RBC transfusions.

Erythropoiesis-stimulating agent-safety issues include thromboembolic events and concerns regarding whether ESAs increase disease progression and/or mortality in cancer patients. Several trials have reported an association between ESA use and increased disease progression and/or mortality, whereas other trials in the same tumour types have not provided similar findings.

This review thoroughly examines available evidence regarding whether ESAs affect disease progression. Both clinical-trial data on ESAs and disease progression, and preclinical data on how ESAs could affect tumour growth are summarised. Preclinical topics include (i) whether tumour cells express EpoR and could be directly stimulated to grow by ESA exposure and (ii) whether endothelial cells express EpoR and could be stimulated by ESA exposure to undergo angiogenesis and indirectly promote tumour growth.

Although assessment and definition of disease progression vary across studies, the current clinical data suggest that ESAs may have little effect on disease progression in chemotherapy patients, and preclinical data indicate a direct or indirect effect of ESAs on tumour growth is not strongly supported."

"This review summarised results from clinical and preclinical studies that evaluated whether ESAs affect disease progression. Although there are important limitations on the quality and assessment of disease progression in these studies, the current meta-analyses suggest no overall effect of ESAs on disease progression. Several individual studies have shown a potential trend associating ESA use with increased disease progression. This suggests that ESAs may affect disease progression in particular cancer patient populations (e.g., head and neck cancer patients receiving radiotherapy only) and that additional research is needed to define these populations and how ESAs mediate this effect. Although indirect effects on tumours induced by increased RBC production are theoretically possible, preclinical data to date suggest that tumour cells either do not express EpoR or express low levels of EpoR molecules that are non-functional and/or are not present at the cell surface. Overall, the balance of current evidence does not support an effect of ESAs on either activating EpoR on tumour cells or indirectly stimulating disease progression via angiogenesis. Future clinical trials, meta-analyses, and preclinical research should provide additional data to guide evidence-based use of ESAs in cancer patients."

REVIEW ARTICLE Online Open article: Biosimilar agents in oncology/haematology: from approval to practice

Abstract

The regulation of biosimilars is a process that is still developing. In Europe, guidance regarding the approval and use of biosimilars has evolved with the products under consideration. It is now more than 3 years since the first biosimilar agents in oncology support, erythropoiesis-stimulating agents, were approved in the EU. More recently, biosimilar granulocyte colony-stimulating factors have received marketing approval in Europe. This review considers general issues surrounding the introduction of biosimilars and highlights current specific issues pertinent to their use in clinical practice in oncology. Information on marketing approval, extrapolation, labelling, substitution, immunogenicity and traceability of each biosimilar product is important, especially in oncology where patients are treated in repeated therapy courses, often with complicated protocols, and where biosimilars are not used as a unique therapy for replacement of e.g. growth hormone or insulin. While future developments in the regulation of biosimilars will need to address multiple issues, in the interim physicians should remain aware of the inherent differences between biosimilar and innovator products.