Role of biosimilars in neutropenia prevention in cancer patients

Decreasing the neutrophils count in peripheral blood after intensive chemotherapy (CT) dramatically increases the risk of infectious complications.As a consequence, treatment costs significantly increased and patients quality of life reduced. Correction of neutropenia is possible with granulocyte colony stimulating factor (G-CSF) – a human protein produced by recombinant technology and is able to support the survival and proliferation of hematopoietic stem cells. Pharmacoeconomic studies have shown that G-CSF reduces the frequency of hospitalization and antibiotics using, which can reduce the treatment cost. The use of G-CSF allows to reduce early and infection mortality after chemotherapy, providing background to prolonging life especially for the elderly (over 65 years) and debilitated patients. The drug is included in all international recommendations. However, its use in Russia is limited due to high cost.
Part of the policy aimed to reducing protein drugs cost and increase their availability is the creation of biosimilars protein drugs with proven effective. At the same time biosimilars as the original protein molecules are living cells products, causing serious difficulties in achieving their identity. To eliminate the risk of reducing the effectiveness or increase the toxicity, the European Union established regulations for the determination the bioproducts quality, a detailed description of the requirements for pre-clinical and clinical research, as well as the requirements for pharmacovigilance. Registered in the EEC countries G-CSF biosimilars have been first studied in healthy volunteers, and then in controlled clinical trials in comparison with the reference drug. High efficacy of one such G-CSF biosimilars (Zarsio®) was shown in controlled clinical trials of 170 patients with breast cancer receiving intensive chemotherapy with Docetaxel and Doxorubicin. Total in the study only 6 % cases of febrile neutropenia (FN) was registered – all within the first chemotherapy cycle. Hospitalization due to FN was required in 3.5 % of patients, and none of these patients did require therapy in the Intensive Care Unit (ICU). Intravenous antibiotics received only 5.3 % of patients with FN. The average duration of severe neutropenia in first cycle in patients treated Zarsio® was 1.8 days compared with 7 days in the control group without the growth factors support. Expected side effects (musculoskeletal pain, leukocytosis, thrombocytopenia, and headache) were of equal frequency in Zarsio® and Neypogen® groups. Serious adverse events were not observed, as well as deaths in all studies. Since 2009, the drug has been successfully used in oncology and hematology patients, which allowed within the expanded pharmacovigilance conduct a retrospective analysis of the effectiveness of neutropenia prevention after the change from the reference preparation filgrastim (GCSF) – Neypogen® on G-CSF biosimilars Zarsio® in general oncology practice which showed comparable results at a lower treatment cost

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